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Tomas Linder

Tomas Linder
I study metabolic pathways in yeasts in order to discover and characterize new genes involved in the synthesis and breakdown of different compounds. I also develop molecular tools to enable genetic engineering of non-conventional species of yeast.

Research

Yeasts are a polyphyletic group of fungi that predominantly grow as single cells. My research focuses on a taxonomic group of yeasts, the sub-phylum Saccharomycotina, better known as the hemiascomycetes or simply the budding yeasts. This group of some 2,000 currently recognised species includes regular baker’s yeast Saccharomyces cerevisiae as well as the opportunistic pathogen Candida albicans. As of 2018, over 100 species of budding yeasts have had their genomes completely sequenced. Even so, with the exception of S. cerevisiae and C. albicans, the functional annotation of these genomes is virtually non-existent.

I am particularly interested in the start- and end-points of metabolic pathways in yeast cells i.e. the genes involved in (1) the initial assimilation of different carbon, nitrogen and sulfur compounds, and (2) the formation of metabolic end-products such as alcohols, organic acids, esters, lipids, terpenoids etc. Assimilatory pathways are of interest as they allow for the use of cheap and renewable growth substrates (e.g. inedible plant biomass) in biotechnological yeast applications. Many yeasts are also capable of assimilating and degrading toxic chemicals such as petroleum products and pesticides. Similarly, metabolic end-products of yeast metabolism have many uses as alternative fuels and fine chemicals. In nature, such compounds play important roles in stress tolerance, growth inhibition of rivals, quorum sensing, pathogenicity and attracting external vectors (mainly insects). The relative ease of manipulating these yeasts allows for the introduction of foreign genes to produce novel compounds with industrial or medical applications.

Currently I am working on developing new model systems for studying the start- and end-points of yeast metabolism. The commonly used model system S. cerevisiae is not suited to these studies as it only assimilates a very limited range of carbon, nitrogen and sulfur substrates. More suitable candidates include the biotechnology yeasts Scheffersomyces stipitis (previously Pichia stipitis) and Lipomyces starkeyi, which have some of the broadest carbon/nitrogen/sulfur-utilization profiles among the budding yeasts.

Cooperation

Waste2Fish - Turning food waste into yeast biomass for aquaculture feed (Project homepage)
This Formas-funded project (2017-2021) aims to develop a two-step process for the production of yeast biomass from food waste, which is then used as aquaculture feed. Food waste is first converted into acetate using anaerobic digestion. The acetate is then used as a feedstock for the cultivation of yeast. The project is lead by Prof Anna Schnürer.

Background

2017-, adjunct researcher, Department of Molecular Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden

2016, adjunct researcher, Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden

2015, researcher, Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden

2011-2014, assistant professor, Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden (funded by Formas, grant #2010-651)

2010, postdoctoral researcher, Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden (funded by the Swedish Research Council, grant #2009-7695)

2007-2009, postdoctoral researcher, Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, USA (funded by the Swedish Research Council, grant #2007-981)

2007, PhD (Molecular and Cellular Biology), Department of Laboratory Medicine, Karolinska Institute, Huddinge, Sweden (Thesis)

2000, Bachelor of Science (Molecular Biology), University of Newcastle upon Tyne, UK

Supervision

Bachelor students

2016, Lina Alashiri

2015, Henrik Borsch Reniers (Thesis)


PhD students (as assistant supervisor)
2014, Mattias Carlsson (Thesis)

Selected publications

27. Linder T. (2019) Nitrogen Assimilation Pathways in Budding Yeasts. In: Sibirny A. (eds) Non-conventional Yeasts: from Basic Research to Application. Springer, Cham. pp. 197–236. (Link)

26. Linder T. (2019) Taxonomic distribution of cytochrome P450 monooxygenases (CYPs) among the budding yeasts (sub-phylum Saccharomycotina). Microorganisms. 7: E247. (Link)

25. Linder T. (2019) Edible microorganisms—An overlooked technology option to counteract agricultural expansion. Frontiers in Sustainable Food Systems. 3: 32. (Link)

24. Linder T. (2019) Making the case for edible microorganisms as an integral part of a more sustainable and resilient food production system. Food Security. 11: 265–278. (Link)

23. Linder T. (2019) A genomic survey of nitrogen assimilation pathways in budding yeasts (sub‐phylum Saccharomycotina). Yeast. 36: 259–273. (Link)

22. Linder T. (2019) Phenotypical characterisation of a putative ω-amino acid transaminase in the yeast Scheffersomyces stipitis. Archives of Microbiology. 201: 185-192. (Link)

21. Linder T. (2019) Cyanase-independent utilization of cyanate as a nitrogen source in ascomycete yeasts. World Journal of Microbiology and Biotechnology. 35: 3. (Link)

20. Linder T. (2018) Evaluation of the chitin-binding dye Congo red as a selection agent for the isolation, classification and enumeration of ascomycete yeasts. Archives of Microbiology. 200: 671-675. (Link)

19. Linder T. (2018) Development of a yeast heterologous expression cassette based on the promoter and terminator elements of the Eremothecium cymbalariae translational elongation factor 1α (EcTEF1) gene. 3 Biotech. 8: 203. (Link)

18. Linder T. (2018) Assimilation of alternative sulfur sources in fungi. World Journal of Microbiology and Biotechnology. 34: 51. (Link)

17. Linder T. (2018) Genetic redundancy in the catabolism of methylated amines in the yeast Scheffersomyces stipitis. Antonie Van Leeuwenhoek. 111: 401-411. (Link)

16. Defosse⁠ TA, Courdavault⁠ V, Coste⁠ AT, Clastre⁠ M, Dugé de Bernonville T, Godon⁠ C, Vandeputte⁠ P, Lanoue⁠ A, Touzé⁠ A, Linder⁠ T, Droby⁠ S, Rosa⁠ CA, Sanglard⁠ D, d'Enfert⁠ C, Bouchara⁠ JP, Giglioli-Guivarc'h⁠ N, Papon⁠ N. (2018) A standardized toolkit for genetic engineering of CTG clade yeasts. Journal of Microbiological Methods. 144: 152-156. (Link)

15. Linder T. (2017) ATP sulfurylase is essential for the utilisation of sulfamate as a sulfur source in the yeast Komagataella pastoris (syn. Pichia pastoris). Current Microbiology. 74: 1021-1025. (Link)

14. Piper AM, Farnier K, Linder T, Speight R, Cunningham JP. (2017) Two gut-associated yeasts in a tephritid fruit fly have contrasting effects on adult attraction and larval survival. Journal of Chemical Ecology. 43: 891-901. (Link and popular science summary)

13. Linder T. (2016) Utilisation of aromatic organosulfur compounds as sulfur sources by Lipomyces starkeyi CBS 1807. Antonie Van Leeuwenhoek. 109: 1417-1422. (Link)

12. Defosse TA, Mélin C, Clastre M, Besseau S, Lanoue A, Glévarec G, Oudin A, Dugé de Bernonville T, Vandeputte P, Linder T, Bouchara JP, Courdavault V, Giglioli-Guivarc'h N, Papon N. (2016) An additional Meyerozyma guilliermondii IMH3 gene confers mycophenolic acid resistance in fungal CTG clade species. FEMS Yeast Research. 16: fow078. (Link)

11. Linder T. (2014) CMO1 encodes a putative choline monooxygenase and is required for the utilization of choline as the sole nitrogen source in the yeast Scheffersomyces stipitis (syn. Pichia stipitis). Microbiology. 160: 929-940. (Link)

10. Steinhauf D, Rodriguez A, Vlachakis D, Virgo G, Maksimov V, Kristell C, Olsson I, Linder T, Kossida S, Bongcam-Rudloff E, Bjerling P. (2014) Silencing motifs in the Clr2 protein from fission yeast, Schizosaccharomyces pombe. PLoS One. 9: e86948. (Link)

9. Linder T. (2012) Genomics of alternative sulfur utilization in ascomycetous yeasts. Microbiology. 158: 2585-2597. (Link)

8. Elmlund H, Baraznenok V, Linder T, Szilagyi Z, Rofougaran R, Hofer A, Hebert H, Lindahl M, Gustafsson CM. (2009) Cryo-EM reveals promoter DNA binding and conformational flexibility of the general transcription factor TFIID. Structure. 17: 1442-1452. (Link)

7. Linder T, Rasmussen NN, Samuelsen CO, Chatzidaki E, Baraznenok V, Beve J, Henriksen P, Gustafsson CM, Holmberg S. (2008) Two conserved modules of Schizosaccharomyces pombe Mediator regulate distinct cellular pathways. Nucleic Acids Research. 36: 2489-2504. (Link)

6. Linder T, Gustafsson CM. (2008) Molecular phylogenetics of ascomycotal adhesins - a novel family of putative cell-surface adhesive proteins in fission yeasts. Fungal Genetics & Biology. 45: 485-497. (Link)

5. Linder T, Zhu X, Baraznenok V, Gustafsson CM. (2006) The classical srb4-138 mutant allele causes dissociation of yeast Mediator. Biochemical and Biophysical Research Communications. 349: 948-953. (Link)

4. Zhu X, Wirén M, Sinha I, Rasmussen NN, Linder T, Holmberg S, Ekwall K, Gustafsson CM. (2006) Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions. Molecular Cell. 22: 169-178. (Link)

3. Linder T, Park CB, Asin-Cayuela J, Pellegrini M, Larsson NG, Falkenberg M, Samuelsson T, Gustafsson CM. (2005) A family of putative transcription termination factors shared amongst metazoans and plants. Current Genetics. 48: 265-269. (Link)

2. Linder T, Gustafsson CM. (2004) The Soh1/MED31 protein is an ancient component of Schizosaccharomyces pombe and Saccharomyces cerevisiae Mediator. Journal of Biological Chemistry. 279: 49455-49459. (Link)

1. Spåhr H, Khorosjutina O, Baraznenok V, Linder T, Samuelsen CO, Hermand D, Mäkela TP, Holmberg S, Gustafsson CM. (2003) Mediator influences Schizosaccharomyces pombe RNA polymerase II-dependent transcription in vitro. Journal of Biological Chemistry. 278: 51301-51306. (Link)


Contact
Researcher at the Department of Molecular Sciences; Biokemi
Telephone: 018-673210
Postal address:
Institutionen för molekylära vetenskaper
Box 7015
750 07 Uppsala
Visiting address: Almas allé 5, BioCentrum, Uppsala, Uppsala