Table of Contents
- Asymmetric Oxidation
- Biochemistry of lipids and lipoproteins
- Computational chemistry
- DNA replication and genome stability
- Synthetic Flow-Chemistry Group
- Food Science and Technology
- Food Tech and Bioengineering
- Immunobiology of leukocyte activation
- Instrumental analysis
- Microfluidic, Lab-on-a-chip and Smart Analytical technologies
- Molecular neurobiology
- Neuron-astrocyte interactions
- Oil Shale Chemistry
- Plant-pathogen interactions
- Reproductive Biology
- Supramolecular Chemistry
- Sustainable chemistry and engineering
- Plant Genetics
- Wood Chemistry
The need for enantiomerically pure substances in pharmaceuticals, agrochemistry and cosmetics is constantly growing. There are basically three ways to obtain pure enantiomers: separation from natural material; separation from the racemic mixture obtained by synthesis and the use of specific methods for asymmetric synthesis.
Imitation of manual biologically active compounds (such as drugs) in chemist's flasks is a serious challenge. The synthesis of the required enantiomer from simple non-arm starting materials requires knowledge of specific asymmetric synthesis techniques and techniques. The desired configuration of the product results from a chiral agent, which is either a chiral reagent, a chiral substrate, a chiral catalyst, or a chiral auxiliary.
The group’s research in recent years has focused on the possible use of cyclopropanol in the synthesis of bioactive cyclic amino acids, the synthesis of several chlamydocin analogues – the developed method is suitable for bioactive molecular libraries, dearomatization of phenols and naphthols under various conditions, etc.
The research is closely related to the Center of Excellence in Molecular Cell Engineering (CEMCE). Together with Professors A. Merits, M. Karelson and T. Tenson, the bioactivity of various compounds and their possible applications are studied.
Margus Lopp, professor, head research scientist
Eleana Lopušanskaja, engineer
Marek Kõllo, engineer
Kristi Rõuk, engineer
Lopušanskaja, E.; Kooli, A.; Paju, A.; Järving, I.; Lopp, M. (2021). Towards ortho-selective electrophilic substitution/addition to phenolates in anhydrous solvents. Tetrahedron, 131935. DOI: 10.1016/j.tet.2021.131935.
Kõllo, M.; Kasari, M.; Kasari, V.; Pehk, T.; Järving, I.; Lopp, M.; Jõers, A.; Kanger, T. (2021). Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols. Beilstein Journal of Organic Chemistry, 17, 581−588. DOI: 10.3762/bjoc.17.52.
Kananovich, D.; Elek, G. Z.; Lopp, M.; Borovkov, V. (2021). Aerobic Oxidations in Asymmetric Synthesis: Catalytic Strategies and Recent Developments. Frontiers in Chemistry, 9. DOI: 10.3389/fchem.2021.614944.
Ivanova, L.; Rausalu, K.; Ošeka, M.; Kananovich, D. G.; Žusinaite, E.; Tammiku-Taul, J.; Lopp, M.; Merits, A.; Karelson, M. (2021). Novel Analogues of the Chikungunya Virus Protease Inhibitor: Molecular Design, Synthesis, and Biological Evaluation. ACS Omega. DOI: 10.1021/acsomega.1c00625.
Zubrytski, D. M.; Elek, G. Z.; Lopp, M.; Kananovich, D. G. (2020). Generation of Mixed Anhydrides via Oxidative Fragmentation of Tertiary Cyclopropanols with Phenyliodine(III) Dicarboxylates. Molecules, 26 (1), #140. DOI: 10.3390/molecules26010140.
Elek, G. Z.; Koppel, K.; Zubrytski, D. M.; Konrad, N.; Järving, I.; Lopp, M.; Kananovich, D. G. (2019). Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin. Organic Letters, 21 (20), 8473−8478. DOI: 10.1021/acs.orglett.9b03305.
Biochemistry of lipids and lipoproteins
Head: Aivar Lõokene, leading researcher, tel. 56159006, 6204378, email@example.com
Research group members: Järving, Ivar; Villo, Ly; Samel, Nigulas
Doctoral students: Risti, Robert
Postdoctoral researchers: Eek, Priit; Teder, Tarvi; Reimund, Mart;
Key words of the research group: Regulation mechanisms of lipid and lipoprotein metabolism, Biomolecular interactions, Lipases, Lipid analysis.
The main topic of the research group is related to the identification of fundamental aspects of lipid and lipoprotein metabolism. The research is focused on the mechanisms of the regulation of lipases and lipoxygenases. We have competence and experience in the study of the structure and properties of proteins, in the analysis of biomolecular interactions, in enzymology as well as in the analysis of lipids. In our research, we use mass spectrometry, chromatography, calorimetry, surface plasmon resonance and fluorescence-based technologies.
IUT19-9 Structural and regulatory aspects of lipid and lipoprotein metabolism (1.01.2014−31.12.2019), Nigulas Samel.
V17081 In vitro assay of Sulodexide, (16.03.2017−31.08.2018)", Aivar Lõokene
SSGF21017 Regulation mechanisms of lipoprotein lipase activity in human plasma (1.01.2021-31.12.2021), Aivar Lõokene
COVSG34 Novel diagnostic tools for detection of SARS-CoV-2 infection for clinical and point-of-care use (1.01.2020-31.12.2021), Vitali Sõritski
RESTA12 Extending the shelf life of food and ensuring quality and safety (1.07.2020−30.06.2023), Ivar Järving
Research field: 1. Natural sciences 1.6 Biosciences
Application of the research in business: Collaboration with Opocrin SPA (Italy) project 17801.
V17801. Patent: Method for calorimetric determination of the lipoprotein lipase activity in human plasma environment; Owners: Tallinna Tehnikaülikool; Authors: Aivar Lõokene, Mart Reimund, Oleg Kovrov, Gunilla Olivecrona; Priority number: US62/350,747; Priority date: 16.06.2016.
1. Rump A, Risti R, Kristal ML, Reut J, Syritski V, Lookene A, Ruutel BoudinotS. Biochem Biophys Res Commun. 2021;534: 457-460.
2. Villo L, Risti R, Reimund M, Kukk K, Samel N, Lookene A. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865(2):158553.
3. Bhadoria R , Ping K , Lohk C , Järving I , Starkov P. Chem Commun (Camb). 2020 Apr 18;56(30):4216-4219.
4. Teder T, Samel N, Lõhelaid H. Arch Biochem Biophys. 2019;676:108126.
5. Põldemaa K, Lipp M, Järving I, Samel N, Eek P. Biochem Biophys Res Commun. 2019 Oct 29;519(1):81-85
6. Reimund M, Wolska A, Risti R, Wilson S, Sviridov D, Remaley AT, Lookene A. Biochem Biophys Res Commun. 2019;519(1):67-72.
7. Reimund M, Kovrov O, Olivecrona G, Lookene A. J Lipid Res. 2017;58(1):279-288.
8. Mihklepp K, Kivirand K, Juronen D, Lõokene A, Rinken T. Enzyme Microb Technol. 2019;130:109360.
Bioinformatics is inherently an interdisciplinary field of science and combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret biological data and phenomena.
The core research areas of TalTech bioinformatics research group lie in genomics and multi-omic data integration. The skill-set of our research group represents a wide variety: experienced and budding experts on image analysis, machine learning, de novo genomics, transcriptomics, computational models, molecular biology, microbiology, plant biology and virology, and cancer genomics.
At the moment we are involved in several research projects in Estonia and internationally that cover topics such as food microbiology, antimicrobial resistance, tree genomics, berry genomics and cancer genomics.
Our research group is still rather young. As scientists constantly have more understanding of biological organisms and their interactions at the system level, and advancing technology is continuously making detailed data acquisition faster and more affordable, it is important to deliver researchers and students the latest knowledge and abilities to use effective analysis methods. By developing skills needed today, and in future, we aim to do our share in raising the level of research and quality of teaching at TalTech.
Group leader: Professor (asst.) Olli-Pekka Smolander
Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries || INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)
ELIMÄKI Locus Is Required for Vertical Proprioceptive Response in Birch Trees || CURRENT BIOLOGY (2020)
Molecular profile of the rat peri-infarct region four days after stroke: study with MANF || EXPERIMENTAL NEUROLOGY (2020)
Droplet-based digital antibiotic susceptibility screen reveals single-cell clonal heteroresistance in an isogenic bacterial population || SCIENTIFIC REPORTS (2020)
Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates || FRONTIERS IN IMMUNOLOGY (2020)
Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium || NATURE (2019)
Biomedicine lab investigates Helicobacter pylori (HP) and its role in the development of liver diseases. HP is a Gram-negative bacterium living in the hostile environment of the human stomach. About 70% of the adult population in Estonia is infected with HP. The bacterium causes gastritis and peptic ulcers, and, in some cases, gastric cancer. HP can also affect other organs including the liver.
Main research topics include:
• Role of Helicobacter pylori-induced invadosomes in liver damages. We have previously shown that infection with HP induces the formation of invadosomes in hepatocytes. We are currently investigating the mechanism behind this phenomenon using in vitro approach complemented with transcriptome sequencing.
• Clinical aspects of Helicobacter pylori-induced liver diseases. We are using the livers of mice infected with HP to analyse short- and long-term effects of the infection with focus on different markers such as YAP1 and CD44.
• Alteration of gut microbiota by Helicobacter pylori leading to the progression of liver diseases. For this study, we are collecting samples from Estonian patients. Our goal is to characterize Estonian HP strains, their effect on mouth/stomach/gut microbiota and liver.
Members of the research group
Group leader: Pirjo Spuul
PhD students: Olga Smirnova, Kaisa Roots, Sadia Khalid
MSc students: Anastasiia Galitskihh, Johanna Kristina Tamm
BSc student: Liisa Truu
Pirjo Spuul, senior researcher, head of the biomedicine lab
Address: Building of Science, Akadeemia road 15, room 140
Varon, C. et al., (2021). Seminars in Cancer Biology, S1044-579X(21)00219-4. DOI: 10.1016/j.semcancer.2021.08.007
Durán, C. et al., (2021). Nature Communications, 12 (1), #1926. DOI: 10.1038/s41467-021-22135-x
Le Roux-Goglin, E. et al., (2012). European Journal of Cell Biology, 91 (3), 161−170. DOI: 10.1016/j.ejcb.2011.11.003
The main area of the research in professor Tõnis Kanger group is asymmetric organic synthesis. Various methods of catalysis (organo-, metal- and enzymatic catalysis) are used separately or in cooperative manner. Special attention is turned to the increase of efficiency of reactions by using selective catalysts, cascade or one-pot reactions. As a new method, a halogen bond donor catalyzed asymmetric reactions are studied. New reactions will be applied on the synthesis of biologically active compounds and their derivatives. A characteristic feature of the research is the application of the principles of sustainable and green chemistry in asymmetric synthesis. The synthesis is supported by spectroscopic and crystallographic experiments, chromatography and quantum chemical calculations.
Members of the catalysis group are Tõnis Kanger, Kadri Kriis, Andrus Metsala, Kristin Erkman, Aleksandra Murre, Kaarel Hunt, Harry Martõnov and Annette Miller.
Sihtmae, M.; Silm, E.; Kriis, K.; Kahru, A.; Kanger, T. Aminocatalysts are More Environmentally Friendly than Hydrogen-Bonding Catalysts. ChemSusChem, 2022, 15, e202201045. DOI link
Hunt, K. E.; García-Sosa, A. T.; Shalima, T.; Maran, U.; Vilu, R.; Kanger, T. Org. Biomol. Chem., 2022, 20, 4724−4735. DOI link
Kriis, K.; Martõnov, H.; Miller, A.; Erkman, K.; Järving, I.; Kaasik, M.; Kanger, T. Multifunctional Catalysts in the Asymmetric Mannich Reaction of Malononitrile with N-Phosphinoylimines: Coactivation by Halogen Bonding versus Hydrogen Bonding. J. Org. Chem. 2022, 87 (11), 7422−7435. DOI link
Silm, E.; Järving, I.; Kanger, T. Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole. Beilstein Journal of Organic Chemistry 2022, 18, 167−173. DOI link
Murre, A.; Erkman, K.; Järving, I.; Kanger, T. Asymmetric Chemoenzymatic One-Pot Synthesis of α-Hydroxy Half-Esters. ACS Omega 2021, 6, 31, 20686–20698. DOI link
Kimm, M.; Järving, I.; Ošeka, M.; Kanger, T. Asymmetric Organocatalytic [2,3]‐Wittig Rearrangement of Cyclohexanone Derivatives. Eur. J. Org. Chem. 2021, 3113–3120. DOI link
Kaasik, M.; Martõnova, J.; Erkman, K,: Metsala, A.; Järving, I.; Kanger, T. Enantioselective Michael addition to vinyl phosphonates via hydrogen bond-enhanced halogen bond catalysis. Chem. Sci., 2021, 12, 7561-7568. DOI link
Trubitsõn, D.; Martõnova, J.; Kudrjašova, M.; Erkman; K.; Järving, I.; Kanger T. Enantioselective Organocatalytic Michael Addition to Unsaturated Indolyl Ketones. Organic Letters, 2021, 23 (5), 1820−1824. DOI link
Kõllo, M.; Kasari, M.; Kasari, V.; Pehk, T.; Järving, I.; Lopp, M.; Jõers, A.; Kanger, T. Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols. Beilstein Journal of Organic Chemistry 2021, 17, 581−588. DOI link
Trubitsõn, D.; Kanger, T. Enantioselective Catalytic Synthesis of N-alkylated Indoles. Symmetry 2020, 12, 1184. DOI link
Kaasik, M.; Kanger, T. Supramolecular Halogen Bonds in Asymmetric Catalysis. Frontiers in Chemistry 2020, 8, 599064. DOI link
Trubitsõn, D.; Martõnova, J.; Erkman, K.; Metsala, A.; Saame, J.; Kõster, K.; Järving, I.; Leito, I.; Kanger, T. Enantioselective N-Alkylation of Nitroindoles under Phase-Transfer Catalysis. Synthesis 2020, 52, 1047−1059. DOI link
Murre, A.; Erkman, K.; Kaabel, S.; Järving, I.; Kanger, T. Diastereoselective [2,3]-Sigmatropic Rearrangement of N-Allyl Ammonium Ylides. Synthesis 2019, 51, 4183−4197. DOI link
Silm, E.; Kaabel, S.; Järving, I.; Kanger, T. Asymmetric Organocatalytic Michael Addition–Cyclisation Cascade of Cyclopentane-1,2-dione with Alkylidene Malononitriles. Synthesis 2019, 51, 4198−4204. DOI link
Kimm, M.; Ošeka, M.; Kaabel, S.; Metsala, A.; Järving, I.; Kanger, T. [2,3]-Wittig Rearrangement as a Formal Asymmetric Alkylation of α-Branched Ketones. Organic Letters 2019, 21, 13, 4976-4980. DOI link
Kaasik, M.; Metsala, A.; Kaabel, S.; Kriis, K.; Järving, I.; Kanger, T. Halo-1,2,3-triazolium Salts as Halogen Bond Donors for the Activation of Imines in Dihydropyridinone Synthesis. Journal of Organic Chemistry 2019, 84, 4294−4303. DOI link
Kaasik, M.; Kaabel, S.; Kriis, K.; Järving, I.; Kanger, T. Synthesis of Chiral Triazole-Based Halogen Bond Donors. Synthesis 2019, 51, 2128-2135. DOI link
Peterson, A.; Kaasik, M.; Metsala, A.; Järving, I.; Adamson, J.; Kanger, T. Tunable chiral triazole-based halogen bond donors: assessment of donor strength in solution with nitrogen-containing acceptors. RSC Advances 2019, 9, 11718−11721. DOI link
Reitel, K.; Kriis, K.; Järvin, I.; Kanger, T. Study of the asymmetric organocatalyzed [3+2] annulation of cyclopropenone and β-keto ester. Chemistry of Heterocyclic Compounds 2018, 54, 929−933. DOI link
Trubitsõn, D.; Žari, S.; Kaabel, S.; Kudrjashova, M.; Kriis, K.; Järving, I.; Pehk, T.; Kanger, T. Asymmetric Organocatalytic Cascade Synthesis of Tetrahydrofuranyl Spirooxindoles. Synthesis 2018, 50, 314−322. DOI link
Ben Moussa, S.; Lachheb, J.; Gruselle, M.; Maaten, B.; Kriis, K.; Kanger, T.; Tõnsuaadu, K.; Badraoui, B. Calcium, Barium and Strontium apatites: A new generation of catalysts in the Biginelli reaction. Tetrahedron 2017, 73, 6542−6548. DOI link
Metsala, A.; Žari, S.; Kanger, T. Reaction path scans: Aza-Michael reactions of isatin imines. Computational and Theoretical Chemistry 2017, 1117, 30-40. DOI link
Kaasik, M.; Kaabel, S.; Kriis, K.; Järving, J.; Aav, R.; Rissanen, K.; Kanger, T. Synthesis and Characterisation of Chiral Triazole‐Based Halogen‐Bond Donors: Halogen Bonds in the Solid State and in Solution. Chemistry - A European Journal 2017, 23, 7337−7344. DOI link
Ošeka, M.; Kimm, M.; Järving, I.; Lippur, K.; Kanger, T. Two Catalytic Methods of an Asymmetric Wittig [2,3]-Rearrangement. J. Org. Chem. 2017, 82, 2889-2897. DOI link
Kriis, K.; Melnik, T.; Lips, K.; Juhanson, I.; Kaabel, S.; Järving, I.; Kanger, T. Asymmetric Synthesis of 2,3,4-Trisubstituted Piperidines. Synthesis 2017, 49, 604-614. DOI link
Metsala, A.; Žari, S.; Kanger, T. Aza-Michael Reactions of Isatin Imines: Deeper Insight and Origin of the Stereoselectivity. ChemCatChem 2016, 8, 2961-2967. DOI link
Ošeka, M.; Kimm, M.; Kaabel, S.; Järving, I.; Rissanen, K.; Kanger, T. Asymmetric Organocatalytic Wittig [2,3]-Rearrangement of Oxindoles. Org. Lett. 2016, 18, 1358-1361. DOI Link
Paju, A.; Kostomarova, D.; Matkevitš, K.; Laos, M.; Pehk, T.; Kanger, T.; Lopp, M. 3-Alkyl-1,2-cyclopentanediones by Negishi cross-coupling of a 3-bromo-1,2-cyclopentanedione silyl enol ether with alkylzinc reagents: An approach to 2-substituted carboxylic acid γ-lactones, homocitric and lycoperdic acids. Tetrahedron 2015, 71, 9313–9320. DOI Link
Preegel, G.; Ilmarinen, K.; Järving, I.; Kanger, T.; Pehk, T.; Lopp, M. Enantioselective Organocatalytic Michael Addition-Cyclization Cascade of Cyclopentane-1,2-dione with Substituted (E)-2-oxobut-3-enoates. Synthesis 2015, 47, 3805–3812. DOI Link
Lippur, K.; Kaabel, S.; Järving, I.; Rissanen, K.; Kanger, T. CaCl2, Bisoxazoline, and Malonate: A Protocol for an Asymmetric Michael Reaction. J. Org. Chem. 2015, 80, 6336-6341. DOI Link
Kaasik, M.; Noole, A.; Reitel, K.; Järving, I.; Kanger, T. Organocatalytic conjugate addition of cyclopropylacetaldehyde derivatives to nitro olefins: En route to β- and γ-amino acids. Eur. J. Org. Chem. 2015, 1745-1753. DOI Link
Žari, S.; Metsala, A.; Kudrjashova, M.; Kaabel, S.; Järving, I.; Kanger, T. Asymmetric organocatalytic aza-michael reactions of isatin derivatives. Synthesis 2015, 47, 875-886. DOI Link
Kreek, K.; Kriis, K.; Maaten, B.; Uibu, M.; Mere, A.; Kanger, T.; Koel, M. Organic and carbon aerogels containing rare-earth metals: Their properties and application as catalysts. J. Non-Cryst. Solids 2014, 404, 43-48. DOI Link
Maaten, B.; Moussa, J.; Desmarets, C.; Gredin, P.; Beaunier, P.; Kanger, T.; Tõnsuaadu, K.; Villemin, D.; Gruselle, M. Cu-modified hydroxy-apatite as catalyst for Glaser-Hay CC homo-coupling reaction of terminal alkynes. J. Mol. Catal. A 2014, 393, 112-116. DOI Link
Preegel, G.; Noole, A.; Ilmarinen, K.; Järving, I.; Kanger, T.; Pehk, T.; Lopp, M. Enantioselective Organocatalytic Michael Addition of Cyclopentane-1,2-diones to Nitroolefins. Synthesis 2014, 46, 2595–2600. DOI Link
Paju, A.; Kanger, T.; Müürisepp, A.-M.; Aid, T.; Pehk, T.; Lopp, M. Sonogashira cross-coupling of 3-bromo-1,2-diones: An access to 3-alkynyl-1,2-diones. Tetrahedron 2014, 70, 5843-5848. DOI Link
Žari, S.; Kudrjashova, M.; Pehk, T.; Lopp, M.; Kanger, T. Remote activation of the nucleophilicity of isatin. Org. Lett. 2014, 16, 1740-1743. DOI Link
Ošeka, M.; Noole, A.; Žari, S.; Öeren, M.; Järving, I.; Lopp, M.; Kanger, T. Asymmetric diastereoselective synthesis of spirocyclopropane derivatives of oxindole. Eur. J. Org. Chem. 2014, 3599-3606. DOI Link
Noole, A.; Malkov, A.; Kanger, T. Asymmetric organocatalytic synthesis of spiro-cyclopropaneoxindoles. Synthesis 2013, 45, 2520-2524. DOI Link
Noole, A.; Ilmarinen, K.; Järving, I.; Lopp, M.; Kanger, T. Asymmetric synthesis of congested spiro-cyclopentaneoxindoles via an organocatalytic cascade reaction. J. Org. Chem. 2013, 78, 8117-8122. DOI Link
Reitel, K.; Lippur, K.; Järving, I.; Kudrjašova, M.; Lopp, M.; Kanger, T. Asymmetric aminocatalytic Michael addition of cyclopropane-containing aldehydes to nitroalkenes. Synthesis 2013, 45, 2679-2683. DOI Link
Noole, A.; Ošeka, M.; Pehk, T.; Öeren, M.; Järving, I.; Elsegood, M.R.J.; Malkov, A.V.; Lopp, M.; Kanger, T. 3-Chlorooxindoles: Versatile starting materials for asymmetric organocatalytic synthesis of spirooxindoles. Adv. Synth. Catal. 2013, 355, 829-835. DOI Link
Ausmees, K.; Kriis, K.; Pehk, T.; Werner, F.; Järving, I.; Lopp, M.; Kanger, T. Diastereoselective multicomponent cascade reaction leading to [3.2.0]-heterobicyclic compounds. J. Org. Chem. 2012, 77, 10680-10687. DOI Link
Lippur, K.; Tiirik, T.; Kudrjashova, M.; Järving, I.; Lopp, M.; Kanger, T. Amination of quinolones with morpholine derivatives. Tetrahedron 2012, 68, 9550-9555. DOI Link
Noole, A.; Järving, I.; Werner, F.; Lopp, M.; Malkov, A.; Kanger, T. Organocatalytic asymmetric synthesis of 3-chlorooxindoles bearing adjacent quaternary-tertiary centers. Org. Lett. 2012, 14, 4922-4925. DOI Link
Žari, S.; Kailas, T.; Kudrjashova, M.; Öeren, M.; Järving, I.; Tamm, T.; Lopp, M.; Kanger, T. Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones. Beil. J. Org. Chem. 2012, 8, 1452-1457. DOI Link
Reile, I.; Paju, A.; Kanger, T.; Järving, I.; Lopp, M. Cyclopentane-1,2-dione bis(tert-butyldimethylsilyl) enol ether in asymmetric organocatalytic Mukaiyama-Michael reactions. Tetrahedron Lett. 2012, 53, 1476-1478. DOI Link
Reinart-Okugbeni, R.; Ausmees, K.; Kriis, K.; Werner, F.; Rinken, A.; Kanger, T. Chemoenzymatic synthesis and evaluation of 3-azabicyclo[3.2.0]heptane derivatives as dopaminergic ligands. Eur. J. Med. Chem. 2012, 55, 255-261. DOI Link
Noole, A.; Pehk, T.; Järving, I.; Lopp, M.; Kanger, T. Organocatalytic asymmetric synthesis of trisubstituted pyrrolidines via a cascade reaction. Tetrahedron: Asymmetry 2012, 23, 188-198. DOI Link
Gruselle, M.; Kanger, T.; Thouvenot, R.; Flambard, A.; Kriis, K.; Mikli, V.; Traksmaa, R.; Maaten, B.; Tõnsuaadu, K. Calcium hydroxyapatites as efficient catalysts for the Michael C-C bond formation. ACS Catalysis 2011, 1, 1729-1733. DOI Link
Ausmees, K.; Selyutina, A.; Kütt, K.; Lippur, K.; Pehk, T.; Lopp, M.; Žusinaite, E.; Merits, A.; Kanger, T. Synthesis and biological activity of bimorpholine and its carbanucleosid. Nucleos Nucleot Nucl 2011, 30, 897-907. DOI Link
Noole, A.; Borissova, M.; Lopp, M.; Kanger, T. Enantioselective organocatalytic aza-ene-type domino reaction leading to 1,4-dihydropyridines. J. Org. Chem. 2011, 76, 1538-1545. DOI Link
Kriis, K.; Ausmees, K.; Pehk, T.; Lopp, M.; Kanger, T. A novel diastereoselective multicomponent cascade reaction. Org. Lett. 2010, 12, 2230-2233. DOI Link
Laars, M.; Raska, H.; Lopp, M.; Kanger, T. Cyclic amino acid salts as catalysts for the asymmetric Michael reaction. Tetrahedron: Asymmetry 2010, 21, 562-565. DOI Link
Noole, A.; Lippur, K.; Metsala, A.; Lopp, M.; Kanger, T. Enantioselective Henry reaction catalyzed by Cu(II) salt and bipiperidine. J. Org. Chem. 2010, 75, 1313-1316. DOI Link
Uudsemaa, M.; Kanger, T.; Lopp, M.; Tamm, T. pKa calculation for monoprotonated bipiperidine, bimorpholine and their derivatives in H2O and MeCN. Chem. Phys. Lett. 2010, 485, 83-86. DOI Link
Lippur, K.; Elmers, C.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Kanger, T.; Lopp, M. Synthesis of 5,5'-disubstituted bimorpholines. Synth. Commun. 2010, 40, 266-281. DOI Link
Laars, M.; Ausmees, K.; Uudsemaa, M.; Tamm, T.; Kanger, T.; Lopp, M. Enantioselective organocatalytic Michael addition of aldehydes to β-nitrostyrenes. J. Org. Chem. 2009, 3772-3775. DOI Link
Uudsemaa, M.; Laars, M.; Kriis, K.; Tamm, T.; Lopp, M.; Kanger, T. Influence of protonation upon the conformations of bipiperidine, bimorpholine, and their derivatives. Chem Phys. Lett. 2009, 471, 92-96. DOI Link
Laars, M.; Kriis, K.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Kanger, T.; Lopp, M. Structural constraints for C2-symmetric heterocyclic organocatalysts in asymmetric aldol reactions. Tetrahedron: Asymmetry 2008, 19, 641-645. DOI Link
Kanger, T.; Kriis, K.; Laars, M.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Bimorpholine-mediated enantioselective intramolecular and intermolecular aldol condensation. J. Org. Chem. 2007, 72, 5168-5173. DOI Link
Kriis, K.; Laars, M.; Lippur, K.; Kanger, T. Bimorpholines as alternative organocatalysts in asymmetric aldol reactions. Chimia 2007, 61, 232-235. DOI Link
Sulzer-Mossé, S.; Laars, M.; Kriis, K.; Kanger, T.; Alexakis, A. Synthesis and use of 3,3′-bimorpholine derivatives in asymmetric Michael addition and intramolecular aldol reaction. Synthesis 2007, 11, 1729-1732. DOI Link
Aav, R.; Kanger, T.; Pehk, T.; Lopp, M. Synthesis of substituted cyclopentanones from 2-oxabicyclo[3.3.0]oct-6-en- 3-one. Proc. Est. Acad. Sci. Chem. 2007, 56, 3-13. Direct Link
Lippur, K.; Kanger, T.; Kriis, K.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Synthesis of (2S,2′S)-bimorpholine N,N′-quaternary salts as chiral phase transfer catalysts. Tetrahedron: Asymmetry 2007, 18, 137-141. DOI Link
Jõgi, A.; Paju, A.; Pehk, T.; Kailas, T.; Müürisepp, A.-M.; Kanger, T.; Lopp, M. Asymmetric synthesis of 2-aryl-5-oxotetrahydrofuran-2-carboxylic acids. Synthesis 2006, 3031-3036. DOI Link
Kriis, K.; Kanger, T.; Laars, M.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Enantioselective synthesis of Wieland-Miescher ketone through bimorpholine-catalyzed organocatalytic aldol condensation. Synlett 2006, 1699-1702. DOI Link
Paju, A.; Laos, M.; Jõgi, A.; Päri, M.; Jäälaid, R.; Pehk, T.; Kanger, T.; Lopp, M. Asymmetric synthesis of 2-alkyl-substituted 2-hydroxyglutaric acid γ-lactones. Tetrahedron Lett. 2006, 47, 4491-4493. DOI Link
Mossé, S.; Laars, M.; Kriis, K.; Kanger, T.; Alexakis, A. 3,3′-bimorpholine derivatives as a new class of organocatalysts for asymmetric Michael addition. Org. Lett. 2006, 8, 2559-2562. DOI Link
Kanger, T.; Laars, M.; Kriis, K.; Kailas, T.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Anchimeric assistance in the case of vicinal dimesylate: Formation of enantiomeric or meso-bimorpholine. Synthesis 2006, 1853-1857. DOI Link
Kanger, T.; Raudla, K.; Aav, R.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Synthesis and derivatization of bis-nor Wieland-Miescher ketone. Synthesis 2005, 3147-3151. DOI Link
Aav, R.; Kanger, T.; Pehk, T.; Lopp, M. Unexpected reactivity of ethyl 2-(diethylphosphono)propionate toward 2,2-disubstituted-1,3-cyclopentanediones. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180, 1739-1748. DOI Link
Paju, A.; Kanger, T.; Pehk, T.; Eek, M.; Lopp, M. A short enantioselective synthesis of homocitric acid-γ-lactone and 4-hydroxy-homocitric acid-γ-lactones. Tetrahedron 2004, 60, 9081-9084. DOI Link
Kriis, K.; Kanger, T.; Lopp, M. Asymmetric transfer hydrogenation of aromatic ketones by Rh(I)/bimorpholine complexes. Tetrahedron: Asymmetry 2004, 15, 2687-2691. DOI Link
Paju, A.; Kanger, T.; Niitsoo, O.; Pehk, T.; Müürisepp, A.-M.; Lopp, M. Asymmetric oxidation of 3-alkyl-1,2-cyclopentanediones. Part 3: Oxidative ring cleavage of 3-hydroxyethyl-1,2-cyclopentanediones: Synthesis of α-hydroxy-γ-lactone acids and spiro-γ-dilactones. Tetrahedron: Asymmetry 2003, 14, 2393-2399. DOI Link
Kriis, K.; Kanger, T.; Müürisepp, A.-M.; Lopp, M. C2-symmetric bimorpholines as chiral ligands in the asymmetric hydrogenation of ketones. Tetrahedron: Asymmetry 2003, 14, 2271-2275. DOI Link
Kanger, T.; Ausmees, K.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. A comparative study of the synthesis of C2-symmetric chiral 2,2′-biaziridinyls. Synlett 2003, 1055-1057. DOI Link
Paju, A.; Kanger, T.; Pehk, T.; Lindmaa, R.; Müürisepp, A.-M.; Lopp, M. Asymmetric oxidation of 3-alkyl-1,2-cyclopentanediones. Part 2: Oxidative ring cleavage of 3-alkyl-1,2-cyclopentanediones: Synthesis of 2-alkyl-γ-lactone acids. Tetrahedron: Asymmetry 2003, 14, 1565-1573. DOI Link
Paju, A.; Kanger, T.; Pehk, T.; Müürisepp, A.-M.; Lopp, M. Asymmetric oxidation of 3-alkyl-1,2-cyclopentanediones. Part 1: 3-Hydroxylation of 3-alkyl-1,2-cyclopentanediones. Tetrahedron: Asymmetry 2002, 13, 2439-2448. DOI Link
Paju, A.; Kanger, T.; Pehk, T.; Lopp, M. Direct asymmetric α-hydroxylation of 2-hydroxymethyl ketones. Tetrahedron 2002, 58, 7321-7326. DOI Link
Kanger, T.; Kriis, K.; Pehk, T.; Müürisepp, A.-M.; Lopp, M. Asymmetric synthesis of novel C2-symmetric bimorpholines. Tetrahedron: Asymmetry 2002, 13, 857-865. DOI Link
Paju, A.; Kanger, T.; Pehk, T.; Lopp, M. Asymmetric oxidation of 1,2-cyclopentanediones. Tetrahedron Lett. 2000, 41, 6883-6887. DOI Link
Aav, R.; Kanger, T.; Pehk, T.; Lopp, M. Synthesis of the AB-ring of 9,11-secosterols. Synlett 2000, 529-531. DOI Link
Alexakis, A.; Aujard, I.; Kanger, T.; Mangeney, P. (R,R)- and (S,S)-N,N'-dimethyl-1,2-diphenylethylene-1,2-diamine. Org. Synth. 1999, 76, 23-34. DOI Link
Rose-Munch, F.; Gagliardini, V.; Perrotey, A.; Tranchier, J.-P.; Rose, E.; Mangeney, P.; Alexakis, A.; Kanger, T.; Vaissermann, J. Two-step synthesis of homochiral monoaminals of tricarbonylphthalaldehydechromium complex. Chem. Commun. 1999, 2061-2062. DOI Link
Kanger, T.; Kriis, K.; Paju, A.; Pehk, T.; Lopp, M. Asymmetric oxidation of cyclobutanones: Modification of the sharpless catalyst. Tetrahedron: Asymmetry 1998, 9, 4475-4482. DOI Link
Kanger, T.; Niidas, P.; Müürisepp, A.-M.; Pehk, T.; Lopp, M. Synthesis of chiral epoxyalkynes. Tetrahedron: Asymmetry 1998, 9, 2499-2508. DOI Link
Lopp, M.; Paju, A.; Kanger, T.; Pehk, T. Direct asymmetric α-hydroxylation of β-hydroxyketones. Tetrahedron Lett. 1997, 38, 5051-5054. DOI Link
Lopp, M.; Paju, A.; Kanger, T.; Pehk, T. Asymmetric Bayer-Villiger oxidation of cyclobutanones. Tetrahedron Lett. 1996, 37, 7583-7586. DOI Link
Kobzar, G.; Mardla, V.; Kanger, R.; Lopp, M.; Lille, U. Comparison of the Anti-Aggregatory activity of enantiomers of a 15-non-stereogenic carbacyclin analogue MIM706. Pharmacol. Toxicol. 1995, 76, 297-298. DOI Link
Alexakis, A.; Kanger, T.; Mangeney, P.; Rose-Munch, F.; Perrotey, A.; Rose, E. Enantioselective ortho-lithiation of benzaldehyde chromiumtricarbonyl complex. Tetrahedron: Asymmetry 1995, 6, 2135-2138. DOI link
Alexakis, A.; Kanger, T.; Mangeney, P.; Rose-Munch, F.; Perrotey, A.; Rose, E. Enantioselective ortho-Lithiation of Aminals of benzaldehyde chromiumtricarbonyl complex. Tetrahedron: Asymmetry 1995, 6, 47-50. DOI link
Kobzar, G.; Shelkovnikov, S.; Mardla, V.; Savitski, G.; Lopp, M.; Kanger, T.; Lille, U. A 15-nonstereogenic carbocyclic analogue of prostacyclin: Effects on human platelets and uterine artery. J. Lipid Mediat. Cell Sign. 1994, 10, 243-249. Link
Kanger, T.; Liiv, M.; Pehk, T.; Lopp, M. A highly stereoselective synthesis of a new propargylic epoxide: (3R,4S)-1-tert-butyldimethylsilyl-3,4-epoxy-1-pentyne. Synthesis 1993, 91-93. DOI Link
Kanger, T.; Lopp, M.; Muraus, A.; Lohmus, M.; Kobzar, G.; Pehk, T.; Lille, U. Synthesis of a novel, optically active 15-nonstereogenic carbaprostacyclin. Synthesis 1992, 925-927. DOI Link
Lopp, M.; Kanger, T.; Miiraus, A.; Pehka, T.; Lille, Ü. Synthesis of a novel four-carbon chiron - (R)-1-t-butyldimethylsilyl-3,4-epoxy-but-1-yne. Tetrahedron: Asymmetry 1991, 2, 943-944. DOI Link
Kanger, T.; Lopp.; Lille, Ü. Reactions of oxiranes. 2. Effect of protective groups on regioselectivity of oxirane opening in 2,3-epoxybicyclo[3.2.0]heptan-6-ones by lithium alkynide in the presence of boron-trifluoride. Zh. Org. Khim. 1991, 27, 1693-1700.
Kanger, T.; Kabat, M, Viha, E.; Lopp, M.; Lille, Ü. Optically-active synthons for synthesis of prostanoids. 1. Separation of 2-exo-bromine-3-endo-hydroxybicyclo[3.2.0]heptan-6-one enantiomers. Zh. Org. Khim. 1990, 26, 1611-1714.
Lopp, M.; Paju, A.; Kanger, T.; Välimäe, T.; Lille, Ü. Alkynylation of ethylene ketal of 1-chloro-4-bromo-1E-buten-3-one - synthesis of enyne and diene fragments of leukotriene and pheromones. Zh. Org. Khim. 1989, 25, 869-870.
Kanger, T.; Lopp, M.; Lille, Ü. Reactions of Oxiranes. 1. Role of Boron-Trifluoride in alkynation of bicyclic oxiranes. Zh. Org. Khim. 1988, 24, 2543-2546.
Pihl, L.; Kanger, T.; Talvik, A. Kinetic study of ionization of nitroalkanes in mixed solvents. 9. Phenylnitromethane and phenylnitromethane-d2 in aqueous dimethylsulfoxide and aqeous dimethylformamide. Org. React. 1984, 21, 436-440.
Computational chemistry utilizes methods based on quantum physics and molecular mechanics in order to model chemically relevant systems and processes. In our research group we are using mainly density functional theory-based models for studying of reaction mechanisms and molecular structure. Our competencies include modelling of inorganic coordination compounds and weakly bound complexes. Recently we have added molecular mechanics, machine learning and computational fluid dynamics to our arsenal. We utilize a variety of computational chemistry software, eg Gaussian, Orca, Turbomole, CP2K, Amber, Gromacs, etc. In addition to an in-group compute cluster we have access to the ETAIS computing clusters, some of which are located on campus.
We have developed descriptions of molecular systems for machine learning models, which are invariant relative to molecular rotations as well as re-numbering of the atoms. The linearized moment tensor potential model has demonstrated high accuracy, rivalling that of the most accurate coupled-cluster quantum chemical models with a computational cost that is lower by several orders of magnitude.
In collaboration with the supramolecular chemistry group we have studied a class of container molecules known as hemicucurbiturils, more specifically the cyclohexano variety of these. Finished projects include binding of neutral and ionic guests, template-based formation of the host molecule, and mechanisms of the synthesis reactions.
Combination of machine learning, quantum mechanics and molecular mechanics methods is showing promising results in accurate mapping of potential energy surfaces of large inorganic catalyst complexes, which are too large to be studied by standard density functional theory techniques. These developments afford new approaches to studies of mechanisms of catalytic reactions.
Head of the group: Toomas Tamm
PhD students: Aleksandra Zahharova, Hanna-Eliisa Luts, Arian Lopušanski, Işılay Öztürk.
DNA replication and genome stability
DNA replication is an essential process of genome duplication that has to be tightly regulated to ensure that each part of the genome is duplicated once and only once per cell cycle. DNA replication remains one of the main targets of cancer therapies as cancer cells tend to proliferate faster and are generally prone to replication stress. One way to make replication targeting drugs more efficient is to increase the number of replication forks in cancer cells. However, most of the replication initiation research to date has been done using model organisms such as yeast Saccharomyces cerevisiae and Saccharomyces pombe, or Xenopus laevis egg extracts. The human DNA replication system is, as expected, much more complex, and identifying human homologs of replication initiation factors using data from model systems has proven difficult, resulting in the need to re-evaluate every finding from a model system on a case-by-case basis.
The group currently leading research efforts in the following topics: i) The role of DNA polymerase epsilon in replication initiation in human cells, ii) developing a novel system to study DNA replication initiation in human cells based on proximity labelling, iii) the role and order of kinase activities in replication initiation.
Group leader: Tatiana Moiseeva, senior research scientist
Sameera Vipat, PhD student
Syed Shahid Musvi, PhD student
Marleen Mikk, MSc student
Pille Leesmäe, BSc student
Hele Anderspuk, MSc 2022
Sigvard Vällo, BSc 2022
Synthetic Flow-Chemistry Group
The research in the group is focused on the development of new electro- and photochemical transformation in continuous-flow. Our research is multidisciplinary, as we combine modern organic synthesis techniques with chemical engineering in order to achieve high efficiency and sustainability. In electro- and photochemical reactions, electricity or light are used as traceless and green reagents to generate highly reactive species under mild reaction conditions, which gives access to the new reaction pathways. Moreover, the potential to harvest sustainable electricity from solar or wind energy and using daylight directly to perform reactions makes electro- and photochemistry highly attractive. In our group, we perform such transformation not in conventional chemical flask or test tubes, but in specially designed flow photo- and electromicroreactors, where solution of chemicals is continuously pumped through the active reactor zone. Due to the continuous nature of the process, such transformations are easy to scale up merging the gap between academia and chemical industry.
Dr. Maksim Ošeka (Principal Investigator)
Anastasiya Krech (PhD Student)
Anni Kooli (Visiting PhD Student)
Food Science and Technology
Objectives and research topics
We aim to develop and promote healthy foods and healthy diets through basic and applied research and teaching. The amount and composition of foods form the base of a healthy food choice. We combine methods of chemistry, physics, sensorics, biotechnology, nutrition and food safety. Biochemical, physical and microbiological processes are followed during the whole food chain, from production of raw materials to food consumption. The wide range of competences enable to solve different problems and developments of food and biotechnology companies.
One of the most important areas is the development of science-based food technologies to produce higher value-added products. We develop processes improving product quality, process yields or cost-effective production. We are also studying the use of alternative raw materials for novel foods.
We use the following methods to conduct research:
Sensory methods, including SPME-GC/MS olfactometry, odor or liquid fractionation for quantitative analysis of food aroma and in consumer preference studies.
Biological methods in the study of microbial communities in food, processing plants, human gastrointestinal tract and other food systems and in solving related problems. For example, to find links between diet and the gastrointestinal microbiota or to study the metabolism of fibers of colonic bacteria, as well as in the analysis of microorganisms in food.
Classical biotechnology methods, including modern microbial cultivation methods to describe the properties of starter cultures used in fermentation processes, to optimize the production process of starter cultures and to optimize the microbial synthesis of additives used in the food industry. We use the so-called variable static flow cultures that allow high-throughput studies of the effects of environmental parameters on microbial cell growth and synthesis yields of substances of interest.
We use physico-chemical methods in the complex analysis of both food composition and related processes. We use modern methods of instrumental analysis, incl. HPLC, GC, UPLC-MS (/MS). To improve quantity, we use internal standards, including radiolabelled. The microstructure of the food is examined with a light and polarization microscope, the flow properties with a viscometer and the mechanical properties with a texture analyzer. Mathematical methods are used in the statistical analysis of food processes and in the modeling of fermentation processes.
Below are the most important topics of the research group.
Relationships of the gastrointestinal microbiota with human nutrition, metabolism and health
Microbiome research group focuses on the elucidation of relationships between food composition and colon microbiome. Food is a crucial factor to modulate the colon microbiota and through bacterial metabolism promote the health-supporting or disease-activating mechanisms. Metabolism of specific dietary fibres and fibre-associated compounds by faecal microbiota will be studied in microcalorimeter and advanced continuous cultures. For analytics we are using systems biology approach (metagenomics, metabolomics, metaproteomics) to model metabolism of complex consortia and develop artificial transplantation material or next generation probiotics.
Sensory and instrumental analysis of food
We developed methods for studying the development and persistence of food sensory properties: the development of taste and aroma in the process of making spice cured sprats, honey, cider, wine, kvass etc.; to detect the causes of off-flavors and odors in spices, drinks and other products. Sensory analysis is a mandatory part of any food project.
The role of peptides as a nitrogen source for yeasts in food fermentation processes
The efficiency of food fermentation processes, e.g. alcoholic fermentations often depend on availablity of essential nutrients, such as nitrogen compounds. Yeast Assimilable Nitrogen (YAN) is frequently used technological term among industrial fermentation specialists and consists primarily free amino acids and ammonia. Nevertheless, in many instances the raw materials and fermentation nutrients used in alcoholic fermentations consist of peptides that are not taken into account as YAN source, albeit they can be taken up and used by yeast. This is mostly due to the the shortage of knowledge on yeast strains capability to transport peptides, as well as lacking suitable qualitative and quantitative methods for peptides analysis in complex fermentation matrices. The goal of this project is to gain more insights into the role of peptides as the YAN source, including their structural diversity and yeast peptides transporters specificity, as well as develop methods for characterization of peptides composition in complex industrial fermentation matrices, e.g. wort, grape must, yeast autolysates.
Food quality and structure
Food structure, texture and consumer preferences and choices of food are closely linked. Changes in the structure and texture of food due to the raw material, technology or preservation affect consumer expectations. In addition to biological and chemical processes, the quality and preservation of food are also affected by physical processes; such as crystallization, glass transition and diffusion. To control these processes, it is necessary to understand the phase behavior of food systems; the nucleation and growth kinetics of crystals; and how food raw materials, production and storage conditions affect this kinetics. We study the effect of ice binding proteins on ice recrystallization, lactose crystallization in ice cream, and the crystallization kinetics of supersaturated sugar solutions. We also study the effects of different food raw materials, production technologies and storage conditions on the micro- and macrostructure, texture and sensory properties of food products.
Sustainable food system
Food systems part of biosystems affecting the greenhouse gas balance on the earth. A sustainable food system is one that delivers food security and nutrition for all in such a way that the economic, social and environmental bases to generate food security and nutrition for future generation is not compromised (FAO). For that optimization of food waste formation and the valorization of side products is critical. We are running two ResTa – support for R@D activities of resource valorization projects: “Extending the shelf life of food and ensuring its quality and safety” and “Solid phase fermentation processes in food valorization”. First of those involves optimization of storage time of food products and the second one valorization of side products of food production (for example brewers spent grain) using solid state fermentations (SFF). The fundamental question is the environmental impact of i) food side product valorization by solid state fermentation compared to feeding to animals, ii) reducing formation of food waste by extending the storage time iii) what are the practical environmental friendly limits both of those approaches.
Solid state fermentations are considered to be most environmental friendly methods for food valorization. It has been used for thousands of years for production of fermented foods in the orient, using aerobic fermentation with filamentous fungi. By contrast, in Western world it has been used in anaerobic fermentations to alter the sensory properties of bread, meat and cheese. The aim of this project is to apply the SFF of food side products for conversion of those through mycelium growth into meat alternatives, particularly for valorization of spent grain. Particular attention is drawn sensory properties and safety of products. In addition development of modern SFF cultivation systems enables to improve production efficiency of biological control agents.
The growth of microorganisms at low, close to zero temperatures, is an important item causing food spoilage and poisoning. Although, there are several studies on growth of bacteria at low temperatures, the effect of temperature downshift during processing has not been elucidated. If latter is fast enough the cell membrane lipid composition is not able to adapt to new conditions, permeability of protons remains outside the optimal range and cells lose their ability to multiply. The latter is particularly important in preventing growth of Listeria during storage of cold smoked products.
Several organisms produce ice binding proteins (IBP) to prevent membrane damage at subzero temperatures. Those organisms include plants, fish and bacteria. Particularly in last case, the mechanisms of those actions are unknown. Knowing action mechanisms of ISP helps as to develop methods for improving quality and prolonging shelf life of frozen products by IBP treatment.
1. Raba, G.; Adamberg, S.; Adamberg, K. (2021). Acidic pH enhances butyrate production from pectin by faecal microbiota. FEMS Microbiology Letters, May 4;368(7):fnab042.
2. Zweers, S.K.T.; Vene, K. (2021). Odour-Active Compounds in Homemade Kvass. EC Nutrition, 16 (2): 59-73. https://www.ecronicon.com/ecnu/pdf/ECNU-16-00908.pdf
3. Eha, K.; Pehk, T.; Heinmaa, I.; Kaleda, A.; Laos, K. (2021). Impact of short-term heat treatment on the structure and functional properties of commercial furcellaran compared to commercial carrageenans. Heliyon, 7(4):e06640. https://doi.org/10.1016/j.heliyon.2021.e06640
4. Kivima, E.; Tanilas, K.; Martverk, K.; Rosenvald, S.; Timberg, L.; Laos, K. (2021). The Composition, Physicochemical Properties, Antioxidant Activity, and Sensory Properties of Estonian Honeys. Foods, 10(3):511. https://doi.org/10.3390/foods10030511
5. Rosend, J.; Kaleda, A.; Kuldjärv, R.; Arju, G.; Nisamedtinov, I (2020). The effect of apple juice clarification and concentration on cider fermentation and properties of the final product. Foods, 9(10):1401. https://doi.org/10.3390/foods9101401
6. Friedenthal, M.; Eha, K.; Kaleda, A.; Part, N.; Laos, K. (2020). Instability of low-moisture carrageenans as affected by water vapor sorption at moderate storage temperatures. SN Applied Sciences, 2: 243 https://doi.org/10.1007/s42452-020-2032-9
7. Rosend, J.; Kuldjarv, R.; Rosenvald, S.; Paalme, T. (2019). The effects of apple variety, ripening stage, and yeast strain on the volatile composition of apple cider. Heliyon, 5(6): e01953
8. Adamberg, K; Kolk, K; Jaagura, M; Vilu, R; Adamberg, S (2018). The composition and metabolism of faecal microbiota is specifically modulated by different dietary polysaccharides and mucin: an isothermal microcalorimetry study. Beneficial Microbes, 1−14.
9. Kaleda, A.; Tsanev, R.; Klesment, T.; Vilu, R.; Laos, K. (2018). Ice cream structure modification by ice-binding proteins. Food Chemistry, 246, 164-171
10. Seisonen, S.; Vene, K.; Koppel, K. (2016). The current practice in the application of chemometrics for correlation of sensory and gas chromatographic data. Food Chemistry, 210 (1), 530−540.
11. Kevvai, K.; Kütt, M.-L.; Nisamedtinov, I.; Paalme, T. (2016). Simultaneous utilization of ammonia, free amino acids and peptides during fermentative growth of Saccharomyces cerevisiae. Journal of the Institute of Brewing, 122 (1), 110−115.
Food Tech and Bioengineering
We are the Food Tech and Bioengineering lab at the Tallinn University of Technology, Department of Chemistry and Biotechnology. Our research is focused on addressing global challenges of biosustainability, including sustainable production of food and feed, but also biochemicals and materials. We are developing novel bio-based processes where microbial cell factories are used to convert various waste carbon like food- and wood industry waste into value-added products.
Relying on the multi-disciplinary skill-set in our research group, we have established the Design-Build-Test-Learn cycle of cell factory design and bioprocess optimization. We use advanced metabolic modeling for the design of novel cell factories; we develop novel synthetic biology tools for the more efficient engineering of cell factories; and use our lab-scale bioreactor platform for the process characterization and optimization. We are additionally utilizing the advancements of additive manufacturing to develop ’living materials’, which will improve biotechnology-based production processes.
By combining these approaches, we aim to translate fundamental science results in industrial biotechnology applications by constructing more efficient producer cells. Together with our global and local partners, we are developing the whole value chains in the circular economy for the sustainable production of value-added products with minimal waste streams.
Petri-Jaan Lahtvee, Assoc. Professor/PI
Nemailla Bonturi, Senior Researcher
Rahul Kumar, Senior Researcher
Srdjan Gavrilovic, Scientist
Paola Monteiro, PhD student
Alina Rekena, PhD student
Henrique Sepulveda Del Rio, PhD student
Gabriel Luz, PhD student
Inna Lipova, PhD student
Luisa Czamanski, visiting PhD student/Engineer
Juliano Sabedotti, visiting PhD student/Engineer
Lenar Lehtla, Engineer
Andreia Axelrud, Research Engineer
Bonturi N, Pinheiro M.J, Monteiro de Oliveira P, Rusadze E, Eichinger T, Liudžiūtė G, Sabedotti De Biaggi J,Brauer A, Remm M, Alves Miranda E, Ledesma-Amaro R, Lahtvee P.J (2022). Development of a dedicated Golden Gate Assembly platform (RtGGA) for Rhodotorula toruloides. bioRxiv, DOI: 10.1016/j.mec.2022.e00200
Reier K, Lahtvee P.J, Liiv A, Remme J (2022). A conundrum of r-protein stability: unbalanced stoichiometry of r-proteins during stationary phase in Escherichia coli. bioRxiv, DOI: 10.1101/2022.03.02.482697
Monteiro De Oliveira P, Aborneva D, Bonturi N, Lahtvee P.J (2021). Screening and growth characterization of non-conventional yeasts in a hemicellulosic hydrolysate. Front. Bioeng. Biotechnol, DOI: 10.3389/fboe.2021.659472
Sánchez B.J, Lahtvee P.J, Campbell K, Kasvandik S, Yu R, Domenzain I, Zelezniak A, Nielsen J (2021). Benchmarking accuracy and precision of intensity-based absolute quantification of protein abundances in Saccharomyces cerevisiae. Proteomics, DOI: 10.1002/pmic.202000093
Butelmann T, Priks H, Parent Z, Johnston T.G., Tamm T, Nelson A, Lahtvee P.J, Kumar R (2021). Metabolism Control in 3D-Printed Living Materials Improves Fermentation. ACS Applied Bio Materials. DOI: 10.1021/acsabm.1c00754
Illarionov A, Lahtvee P.J, Kumar R (2021) Potassium and sodium salt stress characterization in the yeasts Saccharomyces cerevisiae, Kluyveromyces marxianus, and Rhodotorula toruloides. Appl Environ Microbiol 87:e03100-20. DOI:10.1128/AEM.03100-20
Pinheiro M.J, Bonturi N, Belouah I, Miranda EA, Lahtvee P.J (2020). Xylose Metabolism and the Effect of Oxidative Stress on Lipid and Carotenoid Production in Rhodotorula toruloides: Insights for Future Biorefinery. Front. Bioeng. Biotechnol, DOI: 10.3389/fbioe.2020.01008
Johnston T.G, Fillman J.P, Priks H, Butelmann T, Tamm T, Kumar R, Lahtvee P.J, Nelsson A (2020). Cell‐Laden Hydrogels for Multikingdom 3D Printing. Macromolecular Bioscience, 2000121. DOI: 10.1002/mabi.202000121
Priks H, Butelmann T, Illarionov A, Johnston TG, Fellin C, Tamm T, Nelsson A, Kumar R, Lahtvee P.J (2020). Physical confinement impacts cellular phenotype within living materials. ACS Applied Bio Materials, DOI: 10.1021/acsabm.0c00335
Kumar R, Lahtvee P.J (2020). Proteome overabundance enables respiration but limitation onsets carbon overflow. bioRxiv 2020.02.20.957662, DOI: 10.1101/2020.02.20.957662
Lopes H.J.S, Bonturi N, Miranda E.A (2020). Rhodotorula toruloides Single Cell Oil Production Using Eucalyptus urograndis Hemicellulose Hydrolysate as a Carbon Source. Energies 13(4), 795, DOI: 10.3390/en13040795
Lopes H.J.S, Bonturi N, Kerkhoven E.J, Miranda E.A, Lahtvee P.J (2020). C/N ratio and carbon source-dependent lipid production profiling in Rhodotorula toruloides. Applied Microbiology and Biotechnology, DOI: 10.1007/s00253-020-10386-5
Rocha-Meneses L, Otor O.F, Bonturi N, Orupõld K, Kikas T (2020). Bioenergy Yields from Sequential Bioethanol and Biomethane Production: An Optimized Process Flow. Sustainability, 12, 272. DOI: 10.3390/su12010272
Rocha-Meneses L, Ferreira J.A, Bonturi N, Orupõld K, Kikas T (2019). Enhancing Bioenergy Yields from Sequential Bioethanol and Biomethane Production by Means of Solid-Liquid Separation of the Substrates. Energies, 12, 3683. DOI: 10.3390/en12193683
Lahtvee P.J, Sánchez B.J, Smialowska A, Kasvandik S, Elsemman I, Gatto F, Nielsen J (2017) Absolute quantification of protein and mRNA abundances demonstrate variability in gene-specific translation efficiency in yeast. Cell Systems 4:495-504.e5. DOI: 10.1016/j.cels.2017.03.003
Sánchez B.J, Zhang C, Nilsson A, Lahtvee P.J, Kerkhoven E.J, Nielsen J (2017) Improving the phenotype predictions of a yeast genome-scale metabolic model by incorporating enzymatic constraints. Molecular Systems Biology, 13:935, DOI: 10.15252/msb.20167411
Hermano Santos Diniz R, Villada J.C, Tocantins Alvim MC, Pereira Vidigal P.M, Vieira N.M, Lamas-Maceiras M, Esperanza Cerdán M, González-Siso M.I, Lahtvee P.J, Batista da Silveira W (2017) Transcriptome analysis of the thermotolerant yeast Kluyveromyces marxianus CCT 7735 under ethanol stress. Applied Microbiology and Biotechnology, DOI: 10.1007/s00253-017-8432-0
Babazadeh R, Lahtvee P.J, Adiels CB, Goksör M, Nielsen J, Hohmann S (2017) The yeast osmostress response is carbon source dependent. Scientific Reports, 7, 990. DOI: 10.1038/s41598-017-01141-4
Bonturi N, Crucellob A, Carvalho Vianab A.J, Alves Miranda E (2017) Microbial oil production in sugarcane bagasse hemicellulosic hydrolysate without nutrient supplementation by a Rhodosporidium toruloides adapted strain. Process Biochemistry, 57:16-25. DOI: 10.1016/j.procbio.2017.03.007
Lahtvee P.J, Kumar R, Hallström B.M, Nielsen J (2016) Adaptation to different types of stress converge on mitochondrial metabolism. Molecular Biology of the Cell 27: 2505-2514. DOI: 10.1091/mbc.E16-03-0187
Kerkhoven E.J, Lahtvee P.J, Nielsen J (2015) Applications of computational modeling in metabolic engineering of yeast. FEMS Yeast Research 15: 1-13. DOI: 10.1111/1567-1364.12199
Kumar R, Lahtvee P.J, Nielsen J (2015) Systems biology: Developments and Applications. Molecular Mechanisms in Yeast Carbon Metabolism, Editors: J. Piskur and C. Compagno. 83-96. DOI: 10.1007/978-3-642-55013-3_4
Lahtvee P.J, Seiman A, Arike L, Adamberg K, Vilu R (2014) Protein turnover forms one of the highest maintenance costs in Lactococcus lactis. Microbiology 160: 1501-1512. DOI: 10.1099/mic.0.078089-0
Immunobiology of leukocyte activation
PI: Sirje Rüütel Boudinot, docent, senior researcher Tallinn University of Technology
Department of Chemistry and Biotechnology
PhD students: Airi Rump, Kadri Orro, Roland Martin Teras
Researcher: Viiu Paalme
Non-academical members: Emilia Di Giovanni (Erasmus student from University of Palermo)
Key words: immunregulation, leukocyte activation, RGS16, P2X4, P2X7, Multiple Sclerosis, melanoma, eosinophils, Covid19
Fields of research: Biological Sciences, Medical and health sciences.
Description of the project:
The Immunology group at TTU focuses on the biology of leukocyte activation and its regulation. The control of leukocyte activation is of paramount importance for health, both at steady state and during the immune response, to warrant the resilience of the immune system. Dysfunctions of these critical mechanisms lead to auto-inflammatory and auto-immune diseases and also strongly affect the efficiency of defence against pathogens.
We selected two families of regulators of which functions remain poorly understood, the RGS (Regulator of G protein Signalling; main gene target rgs16) and the purinergic receptors (P2X main targets p2x4 and p2x7). We studied control mechanisms of leukocyte activation mediated by these genes in the context of two pathologies: multiple sclerosis and melanoma. Using a combination of in vitro and in vivo (KO mice) models, we performed gain and loss of function experiments to characterize regulatory mechanisms mediated by our genes of interest. We will also determine how modulating P2X4 receptor activity could development of pro- versus anti-inflammatory phenotype of leukocytes (especially in eosinophils) during viral infection and cancer models. We also followed comparative approaches to understand the importance of these genes in the context of the evolution of the immune system.
Main results in 2021:
We have previously identified that RGS16 is involved in the type I IFN response to viral infections and showed that RGS16 mediates the production of multiple pro inflammatory cytokines in monocytes [Suurväli et al 2015]. Using a RGS16 KO mouse we were able to show that disruption of rgs16 confers an acute sensitivity to LPS, and exacerbate Experimental Autoimmune Encephalomyelitis (EAE), a model of multiple sclerosis (Siimut master thesis, Aitai master thesis, manuscript in preparation Rump et al 2022). We also showed in RGS16 KO mice that the expression of RGS16 by recipient mice inhibited the development of grafted melanoma in vivo. (Teras et al 2018 a]. However, this mechanism was not required for the antitumoral effect of the apoptin protein (ORF3) of the circovirus PCV2, which was based on the induction of apoptosis [Teras et al 2018 b]. In collaboration with PERH we demonstrated an effective melanoma treatment method (Teras et al 2020; and PhD thesis Marina Teras, collaboration with PERH).
Among purinergic receptors, P2X7 is by far the best-known effector of activation during immune responses. We showed that P2X7 receptor resulted from the fusion of a P2X4 similar gene with an exon encoding a ballast domain. (Rump et al, 2020a). We focused on P2X4, a purinergic receptor mainly studied in the nervous system, because its implication in the microglial reaction, and its potential involvement in multiple sclerosis, suggested it could also be important in immunity. We wrote a reviewe where we describe diseases whose physiopathology involves P2X4 receptor signaling and summarize that signalling via P2X4 is highly pH dependent (Kanellopoulos et al 2021). We have now demonstrated that P2X4 is expressed by several leukocyte cell subsets. Strikingly, we identified eosinophils from human PBL as the population expressing the highest level of P2X4. As a new surface marker of human eosinophils, P2X4 appears as a useful target to get insight into their biology (Paalme et al 2019).
We demonstrated that the glycosylation of SARS-CoV-2-NP masks some of its antibody epitopes. In many cases, this can lead to false-negative serological tests. Deglycosylation of SARS-CoV-2-NP increased significantly the number of positive tests (Rump et al 2020b).
We plan to characterize the role of P2X4 in the ATP-mediated activation of eosinophils (also mast cells and basophils), using the tools we have developed in collaboration with Professor Jean Kanellopoulos (University Paris Saclay, France). The genetic diversity of P2X4 in the estonian population, and its functional implications, will be addressed in collaboration with the Estonian genome project (PhD project of Airi Rump, co-supervised with O-P Smolander). We also plan to validate P2X4 receptor as a new marker of eosinophils and explore its relevance for prognosis of COVID severity and evolution.
Sirje Rüütel Boudinot, Associate Professor
Tallinn University of Technology
Department of Chemistry and Biotechnology
J. Suurvali, M. Pahtma, R. Saar, V. Paalme, A. Nutt, T. Tiivel, M. Saaremae, C. Fitting, J.M. Cavaillon, and S. Ruutel Boudinot, RGS16 restricts the pro-inflammatory response of monocytes. Scand J Immunol 81 (2015) 23-30.
M. Teras, E. Viisileht, M. Pahtma-Hall, A. Rump, V. Paalme, P. Pata, I. Pata, C. Langevin, and S. Ruutel Boudinot, Porcine circovirus type 2 ORF3 protein induces apoptosis in melanoma cells. BMC Cancer 18 (2018a) 1237.
Teras M, Rump A, Paalme V, Rüütel Boudinot S: Porcine Circovirus Type2 ORF3 protein induces apoptoses in melanoma cells (abstract 2018- No P.B1.03.15; Page 221; A-1919-ECI) Amsterdam, (2018b): https://www.eci2018.org/fileadmin/user_upload/documents/ECI_2018_Abstra ct_Book_web_21082018.pdf
Paalme, V.; Rump, A.; Mädo, K.; Teras, M.; Truumees, B.; Aitai, H.; Ratas, K.; Bourge, M.; Chiang, C.-S.; Ghalali, A.; Tordjmann, T.; Teras, J.; Boudinot, P.; Kanellopoulos, J.; Rüütel Boudinot, S. (2019). Human peripheral blood eosinophils express high level of the purinergic receptor P2X4. Frontiers in Immunology.10.3389/fimmu.2019.02074
Rump, A.; Smolander, O.-P.; Rüütel Boudinot, S.; Kanellopoulos, J. M; Boudinot, P. (2020). Evolutionary origin of the P2X7 C-ter region: capture of an ancient ballast domain by a P2X4-like gene in ancient jawed vertebrates. Frontiers in Immunology, 11, 113−113. DOI: 10.3389/fimmu.2020a.00113.
Teras, J.; Kroon, H. M.; Thompson, J. F.; Teras, M.; Pata, P.; Mägi, A.; Teras, R. M.; Rüütel Boudinot, S. (2020). First Eastern European Experience of Isolated Limb Infusion for In-Transit Metastatic Melanoma Confined to the Limb: Is it still an Effective Treatment Option in the Modern Era? European Journal of Surgical Oncology. Vol 46, Feb 2020, p272-276.
Rump, A.; Risti, R.; Kristal M.-L.; Reut, J.; Syritski, V.; Lõokene, A., Rüütel Boudinot, S. (2021). Dual ELISA using SARS-CoV-2 N protein produced in E. coli and CHO cells reveals epitope masking by N-glycosylation. Biochemical and Biophysical Research Communications, 534, 457−460. DOI: 10.1016/j.bbrc.2020b.11.060
Kanellopoulos J, Almeida-da-Silva CLC, Rüütel Boudinot S and Ojcius DM (2021) Structural and Functional Features of the P2X4 Receptor: An Immunological Perspective. Front. Immunol. 12:645834. doi: 10.3389/fimmu.2021.645834
Analytical chemistry can be considered an inseparable part of several scientific disciplines. All methods that are concerned with the identification, quantification and characterization of substances in complex matrices are associated with the application of analytical chemistry.
The instrumental analysis research group is engaged in the development and application of modern analytical methods to solving problems that are essential to society (food and environmental safety, identification of prohibited chemicals, drug residues in environment, bioactive substances in food and medicinal plants and their effect on tissues, drugs in clinical probes, micro- and macro-elements in food and natural objects) via the utilization of top-quality analytical instrumentation (gas and liquid chromatography, mass spectrometry, spectroscopy, capillary electrophoresis, etc.). The research group’s activity is thereby focused on ensuring the quality and reliability of the research results and applying different statistical methods to the experiments planning and experimental data processing.
• ECAC – Estonian Centre of Analytical Chemistry is a distributed interdisciplinary scientific research infrastructure for the development and application of modern analytical methods as well as the quality assurance of chemical measurements in research, surveillance and industry laboratories.
• Within the framework of the Estonian Research Council project a universal portable analyser is designed, which combines capillary electrophoretic separation and fluorescence-based detection. In the course of this work methodologies of both probe preparation and separation are developed to identify and quantify different narcotic substances in the saliva.
• The ResTA project is focused on the processing, fractionation and functionalization of lignocellulosic biomass to obtain new smart materials, and characterization of these processes by using different analytical methods.
• In the framework of the international project funded by Environmental Investment Centre the laboratory works on developing technologies for the valorization of mandarine juice pomace wastes with the aim to reduce the fruit juice industry’s footprint and environmental impact in Georgia, by using circular economy principles.
• Witin the premises of Instrumental Analysis laboratory operates also the Accredited Chemical Analysis Laboratory that is aimed at applying cutting-edge scientific technologies in co-working with state institutions and private enetrprises.
The research group is looking for bachelor and postgraduate students to join the lab to carry out their thesis projects. Every year doctoral research topics are also disclosed.
Dr. Merike Vaher, Senior research scientist
Dr. Mihkel Koel, Lead research scientist
Dr. Mihkel Kaljurand, Professor emeritus
Dr. Maria Kulp, Senior research scientist
Dr. Maria Kuhtinskaja, Associate professor
Dr. Jekaterina Mazina-Šinkar, Research scientist
Dr. Piret Saar-Reismaa, Research scientist
Dr. Olga Bragina, Research scientist
Dr. Martin Ruzicka, Postdoctoral researcher
Piia Jõul, Early stage researcher
Tiina Kontson, PhD student
Pille-Riin Laanet, Early stage researcher
Vyacheslav Bolkvadze, PhD student
Kristiina Leiman, Specialist
Professor Peep Palumaa's research group is focused on the studies of the biological role and the regulation of two important transition metals - copper and zinc. Copper is an essential cofactor for more than twenty enzymes crucial for cellular energy production, antioxidative defense, and oxidative metabolism. Zinc is involved in cell metabolism and regulates gene expression as it is a cofactor for more than 200 enzymes and is involved in the structuring of more than 600 transcription factors (zinc finger proteins). Dysregulation of copper and zinc homeostasis occurs in multiple diseases, including Wilson's, Menkes, and Alzheimer's disease.
Metalloproteomics group has been studying copper and zinc metabolism through structural and functional studies of key metalloproteins for a long time. In addition, in the last years, they have been using also different cellular and insect models for researching copper and zinc involvement in Alzheimer's disease, such as cell culture and fruit flies. The expected results will substantially advance the knowledge on copper and zinc metabolism, and facilitate the search for molecular tools for its regulation. This is essential for understanding the cause of Alzheimer's disease and elaboration of an effective strategy for its treatment. The research group has different methods at their disposal - LC-ICP MS for ultrasensitive detection of metals, MALDI MS, spectrofluorometer, FPLC, HPLC, and UHPLC chromatographic systems for working with proteins, etc.
The head of the research group Prof. Peep Palumaa received the Estonian National Research Prize in Chemistry and Molecular Biology in 2011 and the TalTech Best Researcher Prize in 2012. Our students have frequently won prizes for their thesis and publications at competitions for student research organized by Estonian Ministry of Education and Research and by research societies.
The research group expects both master's and bachelor's students to conduct research and write their thesis. Please contact firstname.lastname@example.org .
Peep Palumaa, Tenured Full Professor
Vello Tõugu, Associated Professor
Julia Smirnova, Research Scientist
Andra Noormägi, Engineer
Merlin Sardis, Engineer
Katrina Laks, Engineer
Julia Gavrilova, Engineer
Kristel Metsla, PhD student
Sigrid Kirss, PhD student
Jekaterina Kabin, PhD student
Gertrud Hanna Sildnik, Master's Student
Tatjana Golubeva, Master's Student
1. Kirsipuu, T.; Zadorožnaja, A.; Smirnova, J.; Friedemann, M.; Plitz, T.; Tõugu, V.; Palumaa, P. (2020). Copper(II)-binding equilibria in human blood. Scientific Reports, 10 (1), #5686. DOI: 10.1038/s41598-020-62560-4.
2. Krištal, J.; Metsla, K.; Bragina, O.; Tõugu, V.; Palumaa, P. (2019). Toxicity of Amyloid-β Peptides Varies Depending on Differentiation Route of SH-SY5Y Cells. Journal of Alzheimer's Disease, 879−887. DOI: 10.3233/JAD-190705.
3. Wallin, C.; Friedemann, M.; Sholts, S. B; Noormägi, A.; Svantesson, T.; Jarvet, J.; Roos, P. M.; Palumaa, P.; Gräslund, A.; Wärmländer, S. K. T. S. (2019). Mercury and Alzheimer's disease: Hg(II) ions display specific binding to the amyloid-β peptide and hinder its fibrillization. Biomolecules, 10 (1), 1−23. DOI: 10.3390/biom10010044.
4. Smirnova, J.; Kabin, E.; Järving, I.; Bragina, O.; Tõugu, V.; Plitz, T.; Palumaa, P. (2018). Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. α-Lipoic acid as a potential anti-copper agent. Scientific Reports, 8 (1, 1463), 1−9. DOI: 10.1038/s41598-018-19873-2.
5. Krishtal, J.; Bragina, O.; Metsla, K.; Palumaa, P.; Tõugu, V. (2017). In situ fibrillizing Amyloid-beta 1-42 Induce Neurite Degeneration and Apoptosis of Differentiated SH-SY5Y Cells. PLoS ONE. DOI: 10.1371/journal.pone.0186636.
Brancaccio, D.; Gallo, A.; Mikolajczyk, M.; Zovo, K.; Palumaa, P.; Novellino, E.; Piccioli, M.; Ciofi-Baffoni, S.; Banci, L. (2014). Formation of [4Fe-4S] clusters in the mitochondrial iron-sulfur cluster assembly machinery. Journal of the American Chemical Society, 136, 16240−16250.
Palumaa, P. (2013). Copper chaperones. The concept of conformational control in the metabolism of copper. FEBS Letters, 587 (13), 1902−1910.
Tiiman, Ann; Palumaa, Peep; Tõugu, Vello (2013). The Missing Link in the Amyloid Cascade of Alzheimer's Disease - Metal Ions. Neurochemistry International, 62 (4), 367−378.
Banci, L.; Bertini, I.; Cantini, F.; Kozyreva, T.; Massagni, C.; Palumaa, P.; Rubino, JT.; Zovo, K. (2012). Human superoxide dismutase 1 (hSOD1) maturation through interaction with human copper chaperone for SOD1 (hCCS). Proceedings of the National Academy of Sciences of the United States of America, 109 (34), 13555−13560.
Tõugu, V.; Palumaa, P. (2012). Coordination of zinc ions to the key proteins of neurodegenerative diseases: amyloid-β peptide, APP, α-synuclein and prion protein. Coordination Chemistry Reviews, 256, 2219−2224.
Tõugu, Vello; Tiiman, Ann; Palumaa, Peep (2011). Interactions of Zn(II) and Cu(II) ions with Alzheimer’s amyloid-beta peptide. Metal ion binding, contribution to fibrillization and toxicity. Metallomics, 3, 250−261.10.1039/c0mt00073f.
Zovo, Kairit; Helk, Eneken; Karafin, Ann; Tõugu, Vello; Palumaa, Peep (2010). Label-Free High-Throughput Screening Assay for Inhibitors of Alzheimer’s Amyloid-β Peptide Aggregation Based on MALDI MS. Analytical Chemistry, 82 (20), 8558−8565. DOI: 10.1021/ac101583q.
Banci, L.; Bertini, I.; Ciofi-Baffoni, S.; Kozyreva, T.; Zovo, K.; Palumaa, P. (2010). Affinity gradients drive copper to cellular destinations. Nature, 465 (7298), 645−648. DOI: 10.1038/nature09018.
Microfluidic, Lab-on-a-chip and Smart Analytical technologies
Microfluidic, Lab-on-a-chip and Smart Analytical technologies add miniaturization and automation to biological and chemical applications. Constructing and applying such technologies is multidisciplinary, including the fields of mechanics, IT, engineering, material science, chemistry, biology and many others. Microfluidic, Lab-on-a-chip and Smart Analytical technologies are applied in medical diagnostics, pharmacology, basic molecular biology research, space and nanotechnology research, organic and analytical chemistry, and many other areas.
Group website Youtube video
We host ERASMUS exchange projects, also PhD and postdoc projects. Interested people should contact the key persons below.
Briefly, in our research we currently pursue following main directions:
Droplets for high-throughput assays by Professor Ott Scheler; email@example.com
In here we deal with generation, manipulation and analysis of small (pL-nL sized) water-in-oil droplets that act as tiny test tubes, where biological and chemical reactions take place. We generate droplets with microfluidic or traditional emulsion generation tools. Typical droplet experiment can involve generating and analyzing hundreds of thousands (or even millions) of droplets. In our group we apply droplet technologies for microbial analysis, especially to investigate different aspects of antibiotic susceptibility and resistance in bacteria.
People: Prof. Ott Scheler, Dr. Simona Bartkova, Pille Pata, Immanuel Sanka, Fenella Lucia Sulp, Allar Lillepruun, Maryna Lazouskaya and Saari Anete Loog
Automation for Lab-on-a-Chip applications by Dr. Tamas Pardy; firstname.lastname@example.org
We research and develop highly automated technologies and instrumentation for Lab-on-a-Chip applications. Our focus is on applying industry 4.0 to solving problems in Lab-on-a-Chip: machine learning to discern biological objects, wireless communication between bioanalytical devices, digital manufacturing of instrumentation etc. Our goal is to deliver technologies that are user-friendly and open to everyone.
People: Dr. Tamas Pardy, Professor emeritus Toomas Rang, Nafisat Gyimah, Rauno Jõemaa
Smart Analytics by Dr. Jekaterina Mazina-Šinkar; email@example.com
We join the specialists from various departments, universities, and private sector, aiming to ensure groundbreaking research can be turned into successful business opportunities. Over the last 15 years we have successfully developed various analyzers (TRL6-7) for different partners (e.g. Estonian Police and Border Guard). Our core technologies are Capillary Electrophoresis, Fluorescence, Conductivity, Gas Chromatography, Microfluidics, and other instrumental and analytical techniques. We collaborate with various research groups worldwide, providing our competence for successful participation in Horizon Europe and other various open calls.
People: Dr. Jekaterina Mazina-Šinkar, Dr. Jelena Gorbatšova, Dr. Evelin Halling, Professor emeritus Mihkel Kaljurand, Dr. Merike Vaher, Dr. Martin Ruzicka, Vyacheslav Bolkvadze, Jana Budkovskaja
Visit Drug Hunter Analyzer’ website for more information about drug analysis in oral fluid www.drughunter.eu
Publications: https://orcid.org/0000-0002-2430-0097, https://orcid.org/0000-0002-5903-6337, https://orcid.org/0000-0003-2289-188X
Alumni and visitors
Justyna Gruszka Erasmus+ staff exchange 2022
Katri Kiir BSc 2022
Julia Vetik MSc 2022
Monika Meinberg Gymnasium project 2022
Sophie Carpin Erasmus+ student 2021
Natali Agu Gymnasium project 2021
Adam Opalski Erasmus+ staff exchange 2019
Aap Muromägi Gymnasium project 2020
Toomas Teekivi BSc 2019
Tõnis Timmusk has been studying the nervous system for more than 30 years, of which he has worked at Tallinn University of Technology for almost 20 years. In total, he has published more than 90 publications in high-level international scientific journals.
Today, in the laboratory of molecular neurobiology, we study the molecular basis of gene expression and signal transduction in the nervous system and its pathologies, using both mammalian nerve cells and fruit fly as a model system. We seek to understand how cells interact with each other and how this communication regulates gene expression and the connections between nerve cells – the basis of memory and learning. In addition, we are investigating the causes of one autism spectrum disorder, Pitt-Hopkins syndrome, and are looking for potential treatment possibilities.
We are innovative in our work and use modern molecular and cell biology approaches, such as CRISPR-Cas based (epi)genome modification systems, second and third generation sequencing methods, and the creation of various nervous system cells from embryonic stem cells. We also consider it important to participate in international collaborations with other research laboratories. Our goal is to develop a strong generation of neurobiologists in Estonia and we value critically thinking, motivated and enthusiastic people. The team in the neurobiology laboratory is supportive and we maintain high scientific standards.
You can find out more about the work of our laboratory at the virtual exhibition: https://www.lib.ttu.ee/vn/index_teaduspreemiad.html and at the virtual tour https://youtu.be/qNd77YsjLkI.
Members of the Molecular Neurobiology Laboratory include researchers Mari Palgi, PhD, Jürgen Tuvikene, PhD and Florencia Cabrera Cabrera, PhD; lecturer Richard Tamme, PhD; lab manager Epp Väli, and PhD students Laura Tamberg, Eli-Eelika Esvald, Alex Sirp, Annela Avarlaid, Anastassia Šubina and Carl Sander Kiir.
Tuvikene J., Esvald E.E., Rähni A., Uustalu K., Zhuravskaya A., Avarlaid A., Makeyev E. V. Timmusk T. Intronic enhancer region governs transcript-specific BDNF expression in neurons. eLife, 2021, 10:e65161.
2020 Disease Models and Mechanisms
Tamberg L., Jaago M., Säälik K., Sirp A., Tuvikene J., Shubina A., Kiir C. S., Nurm K., Sepp M., Timmusk T., Palgi M. Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome. Dis Model Mech, 2020, Dis Model Mech, 2020, 13: dmm042747.
2020 Journal of Neuroscience
Esvald, E. E.; Tuvikene, J.; Sirp, A.; Patil, S.; Bramham, C. R.; Timmusk, T. CREB Family Transcription Factors Are Major Mediators of BDNF Transcriptional Autoregulation in Cortical Neurons. Journal of Neuroscience, 2020, 40,1405-1426.
Koppel I., Jaanson K., Klasche A., Tuvikene J., Tiirik T., Pärn A., Timmusk T. Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation. Glia, 2018, 66, 206-216.
2017 Journal of Neuroscience
Sepp M., Vihma H., Nurm K., Urb, M., Page S. C., Roots K., Hark A., Maher B. J., Pruunsild, P., Timmusk T. The intellectual disability and schizophrenia associated transcription factor TCF4 is regulated by neuronal activity and protein kinase A. Journal of Neuroscience, 2017, 37, 10516-10527.
2016 Journal of Neuroscience
Tuvikene J., Pruunsild P., Orav E., Esvald E.E., Timmusk T. AP-1 transcription factors mediate BDNF-positive feedback loop in cortical neurons. Journal of Neuroscience, 2016, 36, 1290-1305.
2016 Journal of Neurochemistry
Vihma H., Luhakooder M., Pruunsild P., Timmusk T. Regulation of different human NFAT isoforms by neuronal activity. Journal of Neurochemistry, 2016, 137, 394-408.
2016 European Journal Medicinal Chemistry
Tammiku-Taul J., Park R., Jaanson K., Luberg K., Dobchev D. A., Kananovich D., Noole A., Mandel M., Kaasik A., Lopp M., Timmusk T., Karelson M. Indole-like Trk receptor antagonists. European Journal Medicinal Chemistry, 2016, 121, 541-552.
2015 Biology Open
Tamberg L, Sepp M, Timmusk T., Palgi M. Introducing Pitt-Hopkins syndrome-associated mutations of TCF4 to Drosophila daughterless. Biol. Open, 2015, 4, 1762-1771.
2015 Journal of Neurochemistry
Koppel I., Tuvikene J., Lekk I., Timmusk T. Efficient use of a translation start codon in BDNF exon I. J. Neurochem., 2015, 134,1015-1025.
2014 Handbook of Experimental Pharmacology
West A. E., Pruunsild P., Timmusk T. Neurotrophins: transcription and translation. Handb. Exp. Pharmacol., 2014, 220, 67-100.
2014 Journal of Biological Chemistry
Kannike K., Sepp M., Zuccato C., Cattaneo E., Timmusk T. Forkhead transcription factor FOXO3a levels are increased in Huntington disease because of overactivated positive autofeedback loop. J. Biol. Chem., 2014, 289, 32845-32857.
Koppel I., Timmusk T. Differential regulation of Bdnf expression in cortical neurons by class-selective histone deacetylase inhibitors. Neuropharmacology, 2013, 75, 106-115.
2012 Human Molecular Genetics
Sepp M., Pruunsild P., Timmusk T. Pitt-Hopkins Syndrome associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant negative effects. Hum. Mol. Genet., 2012, 21, 2873-2888.
2011 PLoS ONE
Sepp M., Kannike K., Eesmaa A., Urb M., Timmusk T. Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing. PLoS ONE, 2011, 6, e22138.
2011 Journal of Neuroscience
Pruunsild P., Sepp M., Orav E., Koppel I., Timmusk T. Identification of cis-elements and transcription factors regulating neuronal activity-dependent transcription of human BDNF gene. J. Neurosci., 2011, 31, 3295-3308.
2010 Journal of Neurochemistry
Luberg K., Wong J., Weickert C.S., Timmusk T. Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development. J. Neurochem., 2010, 113, 952-964.
Pruunsild P, Kazantseva A, Aid T, Palm K, Timmusk T. Dissecting the human BDNF locus: bidirectional transcription, complex splicing and multiple promoters. Genomics, 2007, 90, 397-406.
2007 Journal of Neuroscience Research
Aid T., Kazantseva A., Piirsoo M., Palm K., Timmusk T. Mouse and rat BDNF gene structure and expression revisited. J Neurosci. Res, 2007, 85, 525-535.
Lindholm P., Voutilainen M.H., Laurén J., Peränen J., Leppänen V.M., Andressoo J.O., Lindahl M., Janhunen S., Kalkkinen N., Timmusk T., Tuominen R.K., Saarma M. Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature, 2007, 448, 73- 77.
2003 Nature Genetics
Zuccato, C., Tartari, M., Crotti, A., Goffredo, D., Valenza, M., Conti, L., Cataudella, T., Leavitt, L., Hayden, M. R., Timmusk, T., Rigamonti D., Cattaneo, E. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nature Genetics, 2003, 35, 76-83.
Zuccato, C., Ciammola, A., Rigamonti, D., Leavitt, B. R., Goffredo, D., Conti, L., MacDonald, M. E., Friedlander, R. M., Silani, V., Hayden, M. R., Timmusk, T., Sipione, S., Cattaneo, E. Loss of Huntingtin-Mediated BDNF gene transcription in Huntington's disease. Science, 2001, 293, 493-498.
1999 Journal of Biological Chemistry
Timmusk T., Palm K., Lendahl U., Metsis M. Brain-derived neurotrophic factor expression in vivo is under the control of neuron-restrictive silencer element. J. Biol. Chem., 1999, 274, 1078-1084.
Shieh P. B., Hu S.C., Bobb K., Timmusk T., Ghosh A. Identification of a signaling pathway involved in calcium regulation of BDNF expression. Neuron, 1998, 20, 727-740.
1998 Journal of Neuroscience
Palm K., Belluardo N., Metsis M., Timmusk T. Neuronal expression of zinc finger transcription factor REST/NRSF/XBR gene. J. Neurosci., 1998, 18, 1280-1296.
1995 Journal of Cell Biology
Timmusk T., Lendahl U., Funakoshi H., Arenas E., Persson H., Metsis M. Identification of BDNF promoter regions mediating tissue-specific, axotomy- and neuronal activity-induced expression in transgenic mice. J. Cell Biol., 1995, 128, 185-199.
1993 European Journal of Neuroscience
Timmusk T., Belluardo N., Metsis M., Persson H. Widespread and developmentally regulated expression of neurotrophin-4 mRNA in rat brain and peripheral tissues. Eur. J. Neurosci., 1993, 5, 605-613.
Timmusk T., Palm K., Metsis M., Reintam T., Paalme V., Saarma M., Persson H. Multiple promoters direct tissue-specific expression of the rat BDNF gene. Neuron, 1993, 10, 475-489.
Astrocytes cells are one of the most abundant cell types in the central nervous system (CNS). They fulfil several important roles including ion homeostasis, neurotransmitter uptake and maintenance of the blood-brain barrier. It is known that neurons and astrocytes communicate with each other, using neurotransmitters (called gliotransmitters when coming from the astrocyte side) and other intercellular messengers.
In our group, we are interested in how selective activation of intracellular signaling pathways in either neurons or astrocytes will affect the physiology and gene expression in the other cell type.
To this end, we are using novel genetic tools for cell-specific pathway activation and transcriptome/proteome profiling.
Another topic we are interested in is the role of neurotrophins in non-neuronal cell types such as glial cells and cardiomyocytes.
Members of the group:
Dr. Indrek Koppel
Dr. Florencia Cabrera Cabrera
1: Doron-Mandel E, Koppel I, Abraham O, Rishal I, Smith TP, Buchanan CN, Sahoo
PK, Kadlec J, Oses-Prieto JA, Kawaguchi R, Alber S, Zahavi EE, Di Matteo P, Di
Pizio A, Song DA, Okladnikov N, Gordon D, Ben-Dor S, Haffner-Krausz R, Coppola
G, Burlingame AL, Jungwirth P, Twiss JL, Fainzilber M. The glycine arginine-rich
domain of the RNA-binding protein nucleolin regulates its subcellular
localization. EMBO J. 2021 Sep 13:e107158. doi: 10.15252/embj.2020107158. Epub
ahead of print. PMID: 34515347.
2: Mentrup T, Cabrera-Cabrera F, Schröder B. Proteolytic Regulation of the
Lectin-Like Oxidized Lipoprotein Receptor LOX-1. Front Cardiovasc Med. 2021 Jan
20;7:594441. doi: 10.3389/fcvm.2020.594441. PMID: 33553253; PMCID: PMC7856673.
3: Gradtke AC, Mentrup T, Lehmann CHK, Cabrera-Cabrera F, Desel C, Okakpu D,
Assmann M, Dalpke A, Schaible UE, Dudziak D, Schröder B. Deficiency of the
Intramembrane Protease SPPL2a Alters Antimycobacterial Cytokine Responses of
Dendritic Cells. J Immunol. 2021 Jan 1;206(1):164-180. doi:
10.4049/jimmunol.2000151. Epub 2020 Nov 25. PMID: 33239420.
4: Marvaldi L, Panayotis N, Alber S, Dagan SY, Okladnikov N, Koppel I, Di Pizio
A, Song DA, Tzur Y, Terenzio M, Rishal I, Gordon D, Rother F, Hartmann E, Bader
M, Fainzilber M. Importin α3 regulates chronic pain pathways in peripheral
sensory neurons. Science. 2020 Aug 14;369(6505):842-846. doi:
10.1126/science.aaz5875. PMID: 32792398.
5: Mentrup T, Cabrera-Cabrera F, Fluhrer R, Schröder B. Physiological functions
of SPP/SPPL intramembrane proteases. Cell Mol Life Sci. 2020
Aug;77(15):2959-2979. doi: 10.1007/s00018-020-03470-6. Epub 2020 Feb 12. PMID:
32052089; PMCID: PMC7366577.
6: Urb M, Anier K, Matsalu T, Aonurm-Helm A, Tasa G, Koppel I, Zharkovsky A,
Timmusk T, Kalda A. Glucocorticoid Receptor Stimulation Resulting from Early
Life Stress Affects Expression of DNA Methyltransferases in Rat Prefrontal
Cortex. J Mol Neurosci. 2019 May;68(1):99-110. doi: 10.1007/s12031-019-01286-z.
Epub 2019 Mar 9. PMID: 30852742.
7: Mentrup T, Theodorou K, Cabrera-Cabrera F, Helbig AO, Happ K, Gijbels M,
Gradtke AC, Rabe B, Fukumori A, Steiner H, Tholey A, Fluhrer R, Donners M,
Schröder B. Atherogenic LOX-1 signaling is controlled by SPPL2-mediated
intramembrane proteolysis. J Exp Med. 2019 Apr 1;216(4):807-830. doi:
10.1084/jem.20171438. Epub 2019 Feb 28. PMID: 30819724; PMCID: PMC6446863.
8: Koppel I, Fainzilber M. Omics approaches for subcellular translation studies.
Mol Omics. 2018 Dec 3;14(6):380-388. doi: 10.1039/c8mo00172c. PMID: 30338329.
9: Rozenbaum M, Rajman M, Rishal I, Koppel I, Koley S, Medzihradszky KF, Oses-
Prieto JA, Kawaguchi R, Amieux PS, Burlingame AL, Coppola G, Fainzilber M.
Translatome Regulation in Neuronal Injury and Axon Regrowth. eNeuro. 2018 May
10;5(2):ENEURO.0276-17.2018. doi: 10.1523/ENEURO.0276-17.2018. PMID: 29756027;
10: Terenzio M, Koley S, Samra N, Rishal I, Zhao Q, Sahoo PK, Urisman A, Marvaldi
L, Oses-Prieto JA, Forester C, Gomes C, Kalinski AL, Di Pizio A, Doron-Mandel E,
Perry RB, Koppel I, Twiss JL, Burlingame AL, Fainzilber M. Locally translated
mTOR controls axonal local translation in nerve injury. Science. 2018 Mar
23;359(6382):1416-1421. doi: 10.1126/science.aan1053. PMID: 29567716; PMCID:
11: Koppel I, Jaanson K, Klasche A, Tuvikene J, Tiirik T, Pärn A, Timmusk T.
Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF
expression, CREB signaling and morphological transformation. Glia. 2018
Jan;66(1):206-216. doi: 10.1002/glia.23238. Epub 2017 Oct 6. PMID: 28983964.
12: Jaagura M, Taal K, Koppel I, Tuvikene J, Timmusk T, Tamme R. Rat NEURL1 3'UTR
is alternatively spliced and targets mRNA to dendrites. Neurosci Lett. 2016 Dec
2;635:71-76. doi: 10.1016/j.neulet.2016.10.041. Epub 2016 Oct 22. PMID:
13: Tucci P, Estevez V, Becco L, Cabrera-Cabrera F, Grotiuz G, Reolon E, Marín M.
Identification of Leukotoxin and other vaccine candidate proteins in a
<i>Mannheimia haemolytica</i> commercial antigen. Heliyon. 2016 Sep
19;2(9):e00158. doi: 10.1016/j.heliyon.2016.e00158. PMID: 27699279; PMCID:
14: Fernández-Calero T, Cabrera-Cabrera F, Ehrlich R, Marín M. Silent
Polymorphisms: Can the tRNA Population Explain Changes in Protein Properties?
Life (Basel). 2016 Feb 17;6(1):9. doi: 10.3390/life6010009. PMID: 26901226;
15: Koppel I, Tuvikene J, Lekk I, Timmusk T. Efficient use of a translation start
codon in BDNF exon I. J Neurochem. 2015 Sep;134(6):1015-25. doi:
10.1111/jnc.13124. Epub 2015 Apr 27. PMID: 25868795.
16: Garcia-Silva MR, Sanguinetti J, Cabrera-Cabrera F, Franzén O, Cayota A. A
particular set of small non-coding RNAs is bound to the distinctive Argonaute
protein of Trypanosoma cruzi: insights from RNA-interference deficient
organisms. Gene. 2014 Apr 1;538(2):379-84. doi: 10.1016/j.gene.2014.01.023. Epub
2014 Jan 23. PMID: 24463018.
17: Garcia-Silva MR, Cabrera-Cabrera F, das Neves RF, Souto-Padrón T, de Souza
W, Cayota A. Gene expression changes induced by Trypanosoma cruzi shed
microvesicles in mammalian host cells: relevance of tRNA-derived halves. Biomed
Res Int. 2014;2014:305239. doi: 10.1155/2014/305239. Epub 2014 Apr 9. PMID:
24812611; PMCID: PMC4000953.
18: Koppel I, Timmusk T. Differential regulation of Bdnf expression in cortical
neurons by class-selective histone deacetylase inhibitors. Neuropharmacology.
2013 Dec;75:106-15. doi: 10.1016/j.neuropharm.2013.07.015. Epub 2013 Aug 2.
19: Garcia-Silva MR, das Neves RF, Cabrera-Cabrera F, Sanguinetti J, Medeiros LC,
Robello C, Naya H, Fernandez-Calero T, Souto-Padron T, de Souza W, Cayota A.
Extracellular vesicles shed by Trypanosoma cruzi are linked to small RNA
pathways, life cycle regulation, and susceptibility to infection of mammalian
cells. Parasitol Res. 2014 Jan;113(1):285-304. doi: 10.1007/s00436-013-3655-1.
Epub 2013 Nov 17. PMID: 24241124.
20: Garcia-Silva MR, Cabrera-Cabrera F, Güida MC, Cayota A. Hints of tRNA-Derived
Small RNAs Role in RNA Silencing Mechanisms. Genes (Basel). 2012 Oct
10;3(4):603-14. doi: 10.3390/genes3040603. PMID: 24705078; PMCID: PMC3899978.
21: Pruunsild P, Sepp M, Orav E, Koppel I, Timmusk T. Identification of cis-
elements and transcription factors regulating neuronal activity-dependent
transcription of human BDNF gene. J Neurosci. 2011 Mar 2;31(9):3295-308. doi:
10.1523/JNEUROSCI.4540-10.2011. PMID: 21368041; PMCID: PMC6623925.
22: Koppel I, Aid-Pavlidis T, Jaanson K, Sepp M, Palm K, Timmusk T. BAC
transgenic mice reveal distal cis-regulatory elements governing BDNF gene
expression. Genesis. 2010 Apr;48(4):214-9. doi: 10.1002/dvg.20606. PMID:
20186743; PMCID: PMC2978326.
23: Koppel I, Aid-Pavlidis T, Jaanson K, Sepp M, Pruunsild P, Palm K, Timmusk T.
Tissue-specific and neural activity-regulated expression of human BDNF gene in
BAC transgenic mice. BMC Neurosci. 2009 Jun 25;10:68. doi:
10.1186/1471-2202-10-68. PMID: 19555478; PMCID: PMC2708170.
24: Mällo T, Kõiv K, Koppel I, Raudkivi K, Uustare A, Rinken A, Timmusk T, Harro
J. Regulation of extracellular serotonin levels and brain-derived neurotrophic
factor in rats with high and low exploratory activity. Brain Res. 2008 Feb
15;1194(5):110-7. doi: 10.1016/j.brainres.2007.11.041. Epub 2007 Dec 4. PMID:
18177844; PMCID: PMC2568862.
25: Francks C, Maegawa S, Laurén J, Abrahams BS, Velayos-Baeza A, Medland SE,
Colella S, Groszer M, McAuley EZ, Caffrey TM, Timmusk T, Pruunsild P, Koppel I,
Lind PA, Matsumoto-Itaba N, Nicod J, Xiong L, Joober R, Enard W, Krinsky B,
Nanba E, Richardson AJ, Riley BP, Martin NG, Strittmatter SM, Möller HJ, Rujescu
D, St Clair D, Muglia P, Roos JL, Fisher SE, Wade-Martins R, Rouleau GA, Stein
JF, Karayiorgou M, Geschwind DH, Ragoussis J, Kendler KS, Airaksinen MS,
Oshimura M, DeLisi LE, Monaco AP. LRRTM1 on chromosome 2p12 is a maternally
suppressed gene that is associated paternally with handedness and schizophrenia.
Mol Psychiatry. 2007 Dec;12(12):1129-39, 1057. doi: 10.1038/sj.mp.4002053. Epub
2007 Jul 31. PMID: 17667961; PMCID: PMC2990633
Oil Shale Chemistry
Technological further developing the use of oil shale is strategically important for Estonia both socially and economically. Due to the overproduction of oil in the world and the low oil prices, the establishment of an additional shale oil production plant is currently not reasonable and oil production will continue to depend on the price of oil on the world market, which is not stable.
The oil shale research group deals with the valorization of oil shale by its direct degradation to dicarboxylic acids (DCA) and their derivatives, which in turn are raw materials or components of polymers, paints, lubricants, construction chemical products (polyurethanes and construction foams) and many other special materials. At the market price, DCA is ~ 5-100 times more expensive than shale oil, but the products made from it are even more expensive.
Two new methods of chemical decomposition of oil shale – air oxidation (WAO) and nitric acid oxidation were studied within the project “New technological platform for oil shale kerogen enhancement: partial oxidation and further conversion to valuable dicarboxylic acid derivatives” (Smart Specialization Program). Oxidation with both WAO and nitric acid produces dicarboxylic acids from oil shale and its concentrates.
Currently, the work continues in the framework of the Smart Specialization Program. The aim of the project “Technological Platform for Processing Oil Shale Kerogen into Dicarboxylic Acids” is to promote the new oil shale processing technology and to identify product development opportunities. The project consists of two parts: research, which explores different possibilities for creating a continuous-flow technology, and the second part, which involves product development based on the first result.
Margus Lopp, professor, head research scientist
Jaan Mihkel Uustalu, PhD, chief officer
Kristiina Kaldas, PhD, senior reseacher
Tiina Kontson, PhD, chief officer
Andres Siirde, PhD, chief officer
Birgit Mets, PhD, senior reseacher
Estelle Silm, PhD, chief officer
Kati Muldma, engineer
Simm Aia, engineer
Galina Varlamova, PhD, project assistant
Villem Ödner Koern, engineer
Kaldas, K.; Niidu A.; Preegel, G.; Uustalu, J. M.; Muldma, K.; Lopp, M. (2021). Aspects of kerogen oxidative dissolution in subcritical water using oxygen from air. Oil Shale, 38 (3), 199−214. DOI: 10.3176/oil.2021.3.02.
Veetil, S. K. P.; Rebane, K.; Yoruk, C. R.; Lopp, M.; Trikkel, A.; Hitch, M. (2021) Aqueous mineral carbonation of oil shale mine waste (limestone): A feasibility study to develop a CO 2 capture sorbent. Energy, v. 221. DOI10.1016/j.energy.2021.119895
Puthiya Veetil, S. K.; Rebane, K.; Yörük, C. R.; Lopp, M.; Trikkel, A.; Hitch, M. (2021). Aqueous mineral carbonation of oil shale mine waste (limestone): A feasibility study to develop a CO2 capture sorbent. Energy, #119895. DOI: 10.1016/j.energy.2021.119895.
Kaldas, K.; Preegel, G.; Muldma, K. K.; Lopp, M. (2020). Wet Air Oxidation of Oil Shales: Kerogen Dissolution and Dicarboxylic Acid Formation. American Chemical Society, 5, 35, 22021–22030, pubs.acs.org/doi/10.1021/acsomega.0c01466.
Kaldas, K.; Preegel, G.; Muldma, K.; Lopp, M. (2019). Reactivity of Aliphatic Dicarboxylic Acids in Wet Air Oxidation Conditions. Ind. & Eng. Chem. Res., 58, 25, 10855-10863.
Lopp, M.; Kaldas, K.; Preegel, G.; Muldma, K.; Niidu, A. Põlevkivi kerogeeni oksüdeeriva
lahustamise meetod. Est. Pat. Appl. (2021), EE 2019000020 A 20210215.
We study genetic, molecular and cellular aspects of plant-pathogen interactions. As experimental host plant species, we use different cereals as well as model plants (Arabidopsis thaliana and tobacco).
We identify and characterize, using next-generation sequencing techniques, viruses infecting cereal crops in Estonia and neighbouring countries. We are the coordinators of EUPHRESCO ERA-Net project “Epidemiology and diagnosis of viruses infecting cereal crops”, which gathers together 24 international partner organizations.
We study especially sobemoviruses and are members of ICTV. Thanks to the PARROT project “Emergence and divergence of sobemoviruses“, we have reinforced our cooperation with the French National Research Institute for Sustainable Development.
In plant molecular biology, we do research on ABCE proteins that are involved in translation and RNA silencing suppression.
We take part in an EEA-RESEARCH-64 project entitled “Improving adaptability and resilience of perennial ryegrass for safe and sustainable food systems through CRISPR/Cas9 technology (EditGrass4Food)” supported by the European Economic Area and Norway Grants (EEA/Norway). Our partners are the University of Latvia (project coordinator), the Norwegian University of Life Sciences and the Lithuanian Research Centre for Agriculture and Forestry. Perennial ryegrass (Lolium perenne) is the dominant forage grass species in Europe due to its high regrowth capacity and high nutritive value. However, perennial ryegrass exhibits poor performance under unfavourable environmental conditions. Using CRISPR-based editing we validate candidate genes involved in northern adaptation of perennial ryegrass. We focus on genes involved in the mechanisms of freezing tolerance and biomass growth under water deficit. Improving forage production benefits directly dairy and meat industries. Therefore, this project contributes to sustainable food systems.
We coordinate the EMP project entitled “An innovative platform for Estonia-Norway research-based teaching in bioinformatics and gene editing”. Our partner is NMBU. TalTech and NMBU students participated in a bioinformatics course that took place in Norway in May 2022. Next Spring students will attend our course on CRISPR/Cas technologies.
We cooperate with Estonian Crop Research Institute to develop contemporary precision gene editing and genotyping methods (CRISPR/Cas, SSR, KASP, SNPs) for fast and cost-effective genomic selection in barley breeding.
We are part of a project of the Department of Marine Systems that aims to characterise green algae isolated from lakes in Sweden.
As part of “TAIM” (plant biology infrastructure) we offer two services:
- Determination of viral disease agents on plants using the next-generation sequencing
- Genome editing in plants or plant viruses using CRISPR/Cas9 technology
Cecilia Sarmiento – senior researcher, research group leader
Merike Sõmera – senior researcher
Lenne Nigul – engineer
Signe Nõu – engineer
Kairi Kärblane – engineer
Jelena Mõttus – PhD student, engineer
Ferenz Sustek – PhD student, early stage researcher
Anna Ivanova-Pozdejeva – PhD student (together with Estonian Crop Research Institute)
Erki Eelmets – MSc student
Martin Frei – BSc student
Olav Kasterpalu – BSc student
Kristin Antoi – BSc student
Marlene Kaljumäe – BSc student (together with the Department of Marine Systems)
Merits, A.; Abroi, A.; Kurg, R.; Žusinaite, E.; Truve, E.; Sarmiento, C.; Sõmera, M.; Saar, T.; Viltrop, A.; Lutsar, I.; Avi, R.; Karki, T.; Huik, K.; Kõljalg, S.; Brilene, T.; Roots, I.; Inno, H. (2022). Üldine ja Meditsiiniline viroloogia. Tartu: Tartu Ülikooli kirjastus [ilmumas].
Guarino, F.; Cicatelli, A.; Castiglione,S.; Agius, D. R.; Orhun, G. E.; Fragkostefanakis, S.; Leclercq, J.; Dobránszki, J.; Kaiserli, E.; Lieberman-Lazarovich, M.; Sõmera, M.; Sarmiento, C.; Vettori, C.; Paffetti, D.; Poma, A. M. G.; Moschou, P. N.; Gašparović, M.; Yousefi, S.; Vergata, C.; Berger, M. M. J.; Gallusci, P.; Miladinović, D.; Martinelli, F. (2022). An Epigenetic Alphabet of Crop Adaptation to Climate Change. Frontiers in Genetics, 13. DOI:10.3389/fgene.2022.818727
Sõmera, M.; Fargette D.; Hébrard, E.; Sarmiento, C.; ICTV Report Consortium (2021). ICTV Virus Taxonomy Profile: Solemoviridae. Journal of General Virology, 102 (12). DOI: 10.1099/jgv.0.001707.
Sarmiento, C.; Sõmera, M.; Truve, E. (2021). Solemoviruses (Solemoviridae). In: Bamford, D.; Zuckerman, M. (Ed.). Encyclopedia of Virology, 4th edition. Elsevier. DOI: 10.1016/B978-0-12-814515-9.21288-5.
Mõttus, J.; Maiste, S.; Eek, P.; Truve, E.; Sarmiento, C. (2021). Mutational Analysis of Arabidopsis thaliana ABCE2 Identifies Important Motifs for its RNA Silencing Suppressor Function. Plant Biology, 23 (1), 21−31. DOI: 10.1111/plb.13193.
Sõmera, M.; Massart, S.; Tamisier, L.; Sooväli, P.; Sathees, K.; Kvarnheden, A. (2021). A Survey Using High-Throughput Sequencing Suggests That the Diversity of Cereal and Barley Yellow Dwarf Viruses Is Underestimated. Frontiers in Microbiology , 12. DOI: 10.3389/fmicb.2021.673218.
Sõmera, M.; Kvarnheden, A.; Desbiez, C.; Blystad, D.-R.; Sooväli, P.; Kundu, J. K.; Gantsovski, M.; Nygren, J.; Lecoq, H.; Verdin, E.; Spetz, C.; Tamisier, L.; Truve, E.; Massart, S. (2020). Sixty Years after the First Description: Genome Sequence and Biological Characterization of European Wheat Striate Mosaic Virus Infecting Cereal Crops. Phytopathology, 110, 68−79. DOI: 10.1094/PHYTO-07-19-0258-FI.
Infertility is a global problem affecting approximately 15% of all couples in a fertile age. While there are many causes for both male and female infertility, possible treatments are fortunately similarly numerous. One common method enabling otherwise infertile couples to receive genetically their own offspring is in vitro fertilization (IVF). Sadly, the efficiency of IVF is low – on average only one in three procedures culminates in the birth of a child.
The Research Group for Reproductive Biology studies the molecular mechanisms behind fertility and infertility. We are focused foremost on female infertility and on such ovarian processes which assure the maturation of a healthy egg cell. This maturation is affected by hormones from the pituitary gland, steroid hormones produced by the ovaries and several different signaling molecules that move between the egg cell and the granulosa cells surrounding it. By identifying key signaling pathways for egg cell maturation in granulosa cells we can use these cells for diagnostics and thus greatly improve the effectiveness of the IVF procedure.
The ovarian follicle is the main research object in our group. As the oocyte is used for fertilization and embryo development during IVF procedures, invasive methods to study its ingredients are not preferable. However, the environment of oocyte maturation can be evaluated by investigating its surrounding granulosa cells and the follicular fluid that contain a lot of genetic and biochemical information.
In our work we use both classical laboratory methods as well as methods for high throughput analysis (such as analyzing gene expression by deep sequencing, microchip or mass spectrometry methods). In addition, we perform bioinformatical data analysis, biostatistics and modelling signaling pathways.
We are in close cooperation with the Competence Centre on Health Technologies (Tervisetehnoloogia Arenduskeskus AS) and with all fertility clinics in Estonia.
Agne Velthut-Meikas, PhD, Associate professor, principal investigator
Kristine Roos, MSc, PhD student
Inge Varik, MSc, PhD student
Mai-Ly Kristal, BSc, MSc student
Margit Paukson, BSc, MSc student
Katariina Johanna Saretok, BSc student
Cellular, Extracellular and Extracellular Vesicular miRNA Profiles of Pre-Ovulatory Follicles Indicate Signaling Disturbances in Polycystic Ovaries || INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)
Putative adverse outcome pathways for female reproductive disorders to improve testing and regulation of chemicals || ARCHIVES OF TOXICOLOGY (2020)
Safeguarding Female Reproductive Health against Endocrine Disrupting Chemicals-The FREIA Project || INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)
Target prediction and validation of microRNAs expressed from FSHR and aromatase genes in human ovarian granulosa cells || SCIENTIFIC REPORTS (2020)
Supramolecular Chemistry research group is studying intermolecular chemistry, encompassing methods of analytical, organic, and physical chemistry. We are engaged in the development of efficient and environmentally friendly synthetic methods and use them for the preparation of macrocyclic receptor molecules (such as hemicucurbiturils). Development on new mechanochemical synthesis methods is therefore in focus of our interest. Mechanochemistry allows reactions to be performed faster than in dilute solvents and helps to reduce the carbon footprint of chemical processes by avoiding organic solvents. We are studying the formation, structure and properties of nanometer sized macrocyclic molecules. Also, we look for their ability to form complexes and therefore we are routinely applying various quantitative and qualitative analysis methods. We are engaged in the creation of selective receptor molecules that could act as chemosensors for determination of analytes and pollutants, as well as selective absorbents. Since the building blocks of nature are chiral, we focus on chiral molecules. We also study the induction of chirality to molecules giving strong optical signal in low energy regon (e.g., metalloporphyrins). Selective host molecules like macrocycles are useful for development of sensors, sorbents, and regulators of activity of biomolecules.
We routinely perform analysis on following instrumentation (HPLC-UV, HPLC-MS, HRMS, NMR, UV-Vis, IR, FS, SC-XRD). In addition, we analyze the properties of chiral substances by circular dichroism (CD) and vibrational circular dichroism (VCD) spectroscopies.
If you are interested in doing an internship, dissertation or research in our group, please contact the head of the research group Professor Riina Aav (firstname.lastname@example.org), see also our group page:
Group members: Dr. Dzmitry Kananovich, Dr. Victor Borovkov, Dr. Lukaš Ustrnul, Dr. Karin Valmsen, Dr. Marina Kudrjašova, Dr. Elena Prigorchenko (maternity leave), Nele Konrad, Tatsiana Nikonovich, Tatsiana Jarg, Mari-Liis Brük, Jevgenija Martõnova, Marko Šakarašvili, Kristjan Siilak, Jagadeesh Varma, Elina Suut-Tuule, Rauno Reitalu.
1. Dalidovich, T.; Mishra, K. A.; Shalima, T.; Kudrjasova, M.; Kananovich, D. G.; Aav, R. Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents: A Method for Hexa-amidation of Biotinuril. ACS Sustainable Chemistry & Engineering, 2020, 8 (41), 15703-15715. DOI: 10.1021/acssuschemeng.0c05558.
2. Mishra, K.; Adamson, J.; Öeren, M.; Kaabel, S.; Fomitšenko, M.; Aav, R. Dynamic chiral cyclohexanohemicucurbituril, Chemical Communications, 2020, 56, 14645-14648 , DOI: 10.1039/D0CC06817A
3. Kaabel, S.; Stein, R. S.; Fomitsenko, M. Jarving, I.; Friscic, T.; Aav, R. Size-Control by Anion Templating in Mechanochemical Synthesis of Hemicucurbiturils in the Solid State. Angewandte Chemie International Edition. 2019, 58, (19) 6230-6234. DOI: 10.1002/ anie.201813431. Featured on cover
4. Ustrnul, L.; Kaabel, S.; Burankova, T.; Martõnova, J.; Adamson, J.; Konrad, N.; Burk, P.; Borovkov, V.; Aav, R. Supramolecular chirogenesis in zinc porphyrins by enantiopure hemicucurbit[n]urils (n = 6, 8) Chemical Communications, 2019, 55, 14434-14437, DOI: 10.1039/C9CC07150D
5. Kaabel, S.; Adamson, J.; Topic, F.; Kiesila, A.; Kalenius, E.; Oeren, M.; Reimund, M.; Prigorchenko, E.; Lookene, A.; Reich, H. J.; Rissanen, K.; Aav, R. Chiral hemicucurbituril as an anion receptor: selectivity to size, shape and charge distribution. Chemical Science, 2017, 8 (3), 2184-2190. DOI: 10.1039/C6SC05058A.
Sustainable chemistry and engineering
Keywords: Green & Sustainable Chemistry, Functional surfactant self-assembly, Antiviral/ antibacterial formulations, Biodegradability, Biomass valorization, Medicinal chemistry, Chemical decontamination.
Our research activities are focused on designing novel, efficient, safe, and more environmentally benign chemicals and formulations. We target organic chemistry transformations in accordance with the principles of sustainability and green chemistry.
- Organic chemistry application includes development of cleaner organic synthesis methods to obtains small molecules and functional materials for biomedical or environmental applications.
- Medicinal chemistry research includes rational design of antidotes (reactivators of AChE inhibited by OP) and potential anticancer agents (VEGFR and PARP inhibitors). Innovative formulations for drug delivery involve functionalized nanodiamonds and sustainable micro/nanoemulsions.
- Biodegradability facility (OECD 301D CBT) has been installed and used by the team to identify low toxicity or mineralizable transformation products, targeting “benign-by-design” approach.
- Biomass valorisation is resulted in lignin-based surfactants. The novel formulations (micelles, gels, films, or emulsions) are studeid to have tunable antibacterial or antiviral activity.
- Risk management of technogenic accidents includes improvement of (i) antidotal and decontamination formulations for sustainability kits needed for the first responders and volunteers; (ii) disinfectant formulations, which remain at the surface and inactivate bacteria or viruses.
Students of all levels are involved in our research work, including regular traineeships of the international students on individual basis and within networking projects.
PI: Yevgen Karpichev, PhD, Senior Research Scientist (Email: email@example.com )
Group members: Denys Bondar (early-stage researcher/ PhD student), Nandish K. Nagappa (PhD student), Oleg Silenko (early-stage researcher/visiting PhD student), Ella Duvanova (Dora Pluss visiting PhD student), Michael Astorga (DAAD trainee), Munkhtuul Enkhbat (DAAD trainee)
1. Banjare, M. K.; Kamalakanta, B.; Banjare, R. K.; Pandey, S.; Ghosh, K. K.; Karpichev, Y. Molecular Interactions between Novel Synthesized Biodegradable Ionic Liquids with Antidepressant Drug. Chem. Thermodyn. Therm. Anal., 2021 (3-4), 100012. https://doi.org/10.1016/j.ctta.2021.100012
2. Trybrat, O. O.; Yesypenko, O. A.; Shishkina, S. V.; Rusanov, E. B.; Karpichev, Y.; Kalchenko, V. I. (2021). 25-Propyloxy-26,27-dibenzoyloxy-calixarene as Precursor for the Synthesis of Inherently Chiral Calixarenes. Eur. J. Org. Chem., 2021 (28), 3912−3919. DOI: https://doi.org/10.1002/ejoc.202100624
3. Usmani, Z.; Sharma, M.; Karpichev, Y.; Pandey, A.; Kuhad, R.Ch.; Bhat, R.; Poonia, R.; Aghbashlo, M.; Tabatabaei, M.; Gupta, V. K. Advancement in valorization technologies to improve utilization of bio-based waste in bioeconomy context. Renew. Sustain. Energy Rev., 2020 (131), 109965. https://doi.org/10.1016/j.rser.2020.109965 .
4. Velihina, Ye.; Scattolin,Th.; Bondar, D.; Pil'o, S.; Obernikhina, N.; Kachkovskyi, O.; Semenyuta, I.; Caligiuri, I.; Rizzolio, F.; Brovarets, V.; Karpichev, Y.; Nolan S. P. Synthesis, In silico and In vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents. Helv. Chim. Acta, 2020, 103 (12), #e2000169. https://doi.org/10.1002/hlca.202000169
5. Usmani, Z.; Sharma, M.; Gupta, P.; Karpichev, Y.; Gathergood, N.; Bhat, Rajeev; Gupta, V. K. Ionic liquid based pretreatment of lignocellulosic biomass for enhanced bioconversion. Bioresour. Technol., 2020 (304), 123003. https://doi.org/10.1016/j.biortech.2020.123003
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7. Pandya, S.; Kapitanov, I. V.; Usmani, Z.; Sahua, R.; Sinha, D.; Gathergood, N.; Ghosh, K. K.; Karpichev, Y. An Example of Green Surfactant Systems Based on Inherently Biodegradable IL-derived Amphiphilic Oximes. J. Mol. Liquids, 2020 (305), 112857. https://doi.org/10.1016/j.molliq.2020.112857
Informatsioon on täiendamisel
The core laboratory of wood chemistry and biomass valorization technologies unites the laboratories of instrumental analysis, structural biology and lignin biochemistry and the laboratory of sustainable chemistry and technologies under one umbrella with topics related to the development of technologies and strategies for wood and plant biomass valorization. The external collaborative partners of the core lab are Tartu University, Estonian University of Life Sciences as well as the National Institute of Chemical Physics and Biophysics. Additionally, the core group actively collaborates with the Department of Materials and Environmental Technology (Prof. Krumme and Prof. Kers). The research activities of the core lab are coordinated by Dr. Tiit Lukk.
The core laboratory of wood chemistry and biomass valorization technologies carries out interdisciplinary work in the following research areas:
Fractionation and analytical chemistry of wood polymers:
Dr. Maria Kulp – group leader
Karl Romek Staškevitš
Functional materials from wood polymers:
Dr. Mihkel Koel ja Dr. Yevgen Karpichev – group leaders
Dr. Piia Jõul
Mahendra Kothottil Mohan
Biochemical valorization of biomass:
Dr. Tiit Lukk – group leader
Dr. Eve-Ly Ojangu
Dr. Kairit Zovo
Valorization of secondary biomass sources:
Dr. Maria Kuhtinskaja ja Dr. Merike Vaher – group leaders
Dr. Tiit Lukk
MOBTT60 - The role of actinomycete metalloproteins in lignin depolymerization and soil chemistry
RESTA11 - Development of chemical and biochemical valorization technologies for bleached chemithermomechanical pulps (BCTMP) and secondary woody biomass sources.
KIK21023 - Development of technologies for the valorization of mandarin pomace waste with the goal of alleviating the environmental impact of Georgian fruit juice industry while utilizing the principles of circular economy