Mohamed S. Donia
Position
Associate Professor of Molecular Biology
Website
Bio/Description
Focus
Small-molecule-mediated interactions in complex microbial communitiesResearch
Much like human beings, microbes often live in diverse communities interacting with both collaborators and competitors. Small molecule natural products mediate a significant portion of these interactions. As expected, the more complex a microbial community is, the richer its small molecule chemical arsenal becomes. This phenomenon has been observed in the complex microbiomes of marine invertebrates, terrestrial soils, human gut, and the plant rhizosphere, among others. Our research interests are mainly to study the chemical and biological interactions within complex microbial communities (microbe-microbe interactions) and between microbial communities and their multicellular hosts (microbe-host interactions). In respect to the human body and its microbial inhabitants (the human microbiome), these interactions can define the difference between commensals and pathogens, and thus between health and disease states. In the case of marine invertebrates (e.g., sponges and ascidians) and their symbionts, these interactions can provide the host with indispensible means of chemical defense, allowing it to survive in a predator-rich environment. In the soil or seawater, these interactions can dictate the microbial community’s composition, fitness and stability over time. Our ongoing efforts towards understanding these interactions will not only explain fundamentals of basic biology in these systems, but will also supply a suite of biologically active small molecules that can be developed as therapeutic agents.
In addition, the Donia lab has a special interest in the uncultivable microbial components of complex communities, which have eluded research attempts for decades despite their abundance and clear importance. Recent advances in the fields of metagenomics and single-cell genomics have allowed access to the genetic information of some of these unculturable microbes, while functional studies remain challenging. Our goal is to develop the necessary computational and experimental tools to functionally study the interactions mediated by uncultivable members of complex microbiomes, using an integrated multi “omics” approach, including metagenomics, metabolomics and metatranscriptomics. The Donia lab functions at the intersection between multiple disciplines: microbiology, molecular biology, biochemistry, small molecule chemistry and biosynthesis, metagenomics and bioinformatics, aiming to answer basic biological questions and to develop new therapeutics.
Biography
Dr. Donia received his B.Sc in Pharmacy from the Faculty of Pharmacy, Suez Canal University, Egypt in 2004. He moved to the US in 2005 to study for his Ph.D. at the Medicinal Chemistry Department, School of Pharmacy, University of Utah. He worked in Dr. Eric Schmidt's laboratory where he studied the chemistry and biology of small molecules produced by bacterial symbionts of marine animals. He used chemical, microbiological, and metagenomic techniques to study the role of small molecules in mediating microbe-host and microbe-microbe interactions in marine invertebrates. In 2010, he joined Dr. Michael Fischbach's laboratory at the Department of Bioengineering and Therapeutic Sciences at the University of California, San Francisco. There, he studied small molecules produced by members of the human microbiome and their role in mediating microbe-host and microbe-microbe interactions in humans. In particular, he focused on antibiotics produced by human pathogens and commensals, and their role in shaping the composition and dynamics of the human vaginal and oral microbiota.
Honors & Awards
2016
- Breakthrough Award, Kenneth Rainin Foundation
2015
- Innovation Award, Department of Molecular Biology, Princeton University
- New Innovator Award, National Institutes of Health
Education
- B.Sc., Pharmacy, College of Pharmacy, Suez Canal University, Egypt
- Ph.D., Medicinal Chemistry, College of Pharmacy, University of Utah
Selected Publications
- 1.Zeng X, Xing X, Gupta M, Keber F, Lopez J, Lee Y-C, Roichman A, Wang L, Neinast M, Donia M, Wühr M, Jang C, Rabinowitz J. Gut bacterial nutrient preferences quantified in vivo. Cell. 2022;185(18):3441–3456.e19. PMCID: PMC9450212
- 1.Wyer S, Townsend D, Ye Z, Kourtidis A, Choo Y-M, de Barros A, Donia M, Hamann M. Recent advances and limitations in the application of kahalalides for the control of cancer. Biomed Pharmacother. 2022;148:112676. PMCID: PMC9004612
- 1.Lopez J, Donia M, Wingreen N. Modeling the ecology of parasitic plasmids. ISME J. 2021;15(10):2843–2852. PMCID: PMC8443676
- 1.Scheffler R, Sugimoto Y, Bratton B, Ellison C, Koch M, Donia M, Gitai Z. Pseudomonas aeruginosa detachment from surfaces via a self-made small molecule. J Biol Chem. 2021;296:100279. PMCID: PMC7949062
- 1.Lopez J, Donia M, Wingreen N. Publisher Correction: Modeling the ecology of parasitic plasmids. ISME J. 2021;15(12):3722. PMCID: PMC8630101
- 1.Balaich J, Estrella M, Wu G, Jeffrey P, Biswas A, Zhao L, Korennykh A, Donia M. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature. 2021;600(7887):110–115. PMCID: 3552296
- 1.Claesen J, Spagnolo J, Ramos S, Kurita K, Byrd A, Aksenov A, Melnik A, Wong W, Wang S, Hernandez R, Donia M, Dorrestein P, Kong H, Segre J, Linington R, Fischbach M, Lemon K. A antibiotic modulates human skin microbiota composition in hair follicles. Sci Transl Med. 2020;12(570). PMCID: PMC8478231
- 1.Javdan B, Lopez J, Chankhamjon P, Lee Y-C, Hull R, Wu Q, Wang X, Chatterjee S, Donia M. Personalized Mapping of Drug Metabolism by the Human Gut Microbiome. Cell. 2020;181(7):1661–1679.e22. PMCID: PMC8591631
- 1.Liou C, Sirk S, Diaz C, Klein A, Fischer C, Higginbottom S, Erez A, Donia M, Sonnenburg J, Sattely E. A Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont. Cell. 2020;180(4):717–728.e19. PMCID: PMC7515767
- 1.Kloosterman A, Cimermancic P, Elsayed S, Du C, Hadjithomas M, Donia M, Fischbach M, van Wezel G, Medema M. Expansion of RiPP biosynthetic space through integration of pan-genomics and machine learning uncovers a novel class of lanthipeptides. PLoS Biol. 2020;18(12):e3001026. PMCID: PMC7794033
- 1.Farag M, Hegazi N, Donia M. Molecular networking based LC/MS reveals novel biotransformation products of green coffee by ex vivo cultures of the human gut microbiome. Metabolomics. 2020;16(8):86. PMID: 32748036
- 1.Zan J, Li Z, Tianero M, Davis J, Hill R, Donia M. A microbial factory for defensive kahalalides in a tripartite marine symbiosis. Science. 2019;364(6445). PMID: 31196985
- 1.Tianero M, Balaich J, Donia M. Localized production of defence chemicals by intracellular symbionts of Haliclona sponges. Nat Microbiol. 2019;4(7):1149–1159. PMCID: PMC8647704
- 1.Liu M, El-Hossary E, Oelschlaeger T, Donia M, Quinn R, Abdelmohsen U. Potential of marine natural products against drug-resistant bacterial infections. Lancet Infect Dis. 2019;19(7):e237-e245. PMID: 31031171
- 1.Sugimoto Y, Camacho F, Wang S, Chankhamjon P, Odabas A, Biswas A, Jeffrey P, Donia M. A metagenomic strategy for harnessing the chemical repertoire of the human microbiome. Science. 2019;366(6471). PMID: 31582523
- 1.Tuttle R, Demko A, Patin N, Kapono C, Donia M, Dorrestein P, Jensen P. Detection of Natural Products and Their Producers in Ocean Sediments. Appl Environ Microbiol. 2019;85(8). PMCID: PMC6450032
- 1.Guo C-J, Chang F-Y, Wyche T, Backus K, Acker T, Funabashi M, Taketani M, Donia M, Nayfach S, Pollard K, Craik C, Cravatt B, Clardy J, Voigt C, Fischbach M. Discovery of Reactive Microbiota-Derived Metabolites that Inhibit Host Proteases. Cell. 2017;168(3):517–526.e18. PMCID: PMC5302092
- 1.Cervantes-Barragan L, Chai J, Tianero M, Di Luccia B, Ahern P, Merriman J, Cortez V, Caparon M, Donia M, Gilfillan S, Cella M, Gordon J, Hsieh C-S, Colonna M. induces gut intraepithelial CD4CD8αα T cells. Science. 2017;357(6353):806–810. PMCID: PMC5687812
- 1.Medema M, Kottmann R, Yilmaz P, Cummings M, Biggins J, Blin K, de Bruijn I, Chooi Y, Claesen J, Coates C, Cruz-Morales P, Duddela S, Düsterhus S, Edwards D, Fewer D, Garg N, Geiger C, Gomez-Escribano J, Greule A, Hadjithomas M, Haines A, Helfrich E, Hillwig M, Ishida K, Jones A, Jones C, Jungmann K, Kegler C, Kim H, Kötter P, Krug D, Masschelein J, Melnik A, Mantovani S, Monroe E, Moore M, Moss N, Nützmann H-W, Pan G, Pati A, Petras D, Reen J, Rosconi F, Rui Z, Tian Z, Tobias N, Tsunematsu Y, Wiemann P, Wyckoff E, Yan X, Yim G, Yu F, Xie Y, Aigle B, Apel A, Balibar C, Balskus E, Barona-Gómez F, Bechthold A, Bode H, Borriss R, Brady S, Brakhage A, Caffrey P, Cheng Y-Q, Clardy J, Cox R, De Mot R, Donadio S, Donia M, van der Donk W, Dorrestein P, Doyle S, Driessen A, Ehling-Schulz M, Entian K-D, Fischbach M, Gerwick L, Gerwick W, Gross H, Gust B, Hertweck C, Höfte M, Jensen S, Ju J, Katz L, Kaysser L, Klassen J, Keller N, Kormanec J, Kuipers O, Kuzuyama T, Kyrpides N, Kwon H-J, Lautru S, Lavigne R, Lee C, Linquan B, Liu X, Liu W, Luzhetskyy A, Mahmud T, Mast Y, Méndez C, Metsä-Ketelä M, Micklefield J, Mitchell D, Moore B, Moreira L, Müller R, Neilan B, Nett M, Nielsen J, O’Gara F, Oikawa H, Osbourn A, Osburne M, Ostash B, Payne S, Pernodet J-L, Petricek M, Piel J, Ploux O, Raaijmakers J, Salas J, Schmitt E, Scott B, Seipke R, Shen B, Sherman D, Sivonen K, Smanski M, Sosio M, Stegmann E, Süssmuth R, Tahlan K, Thomas C, Tang Y, Truman A, Viaud M, Walton J, Walsh C, Weber T, van Wezel G, Wilkinson B, Willey J, Wohlleben W, Wright G, Ziemert N, Zhang C, Zotchev S, Breitling R, Takano E, Glöckner F. Minimum Information about a Biosynthetic Gene cluster. Nat Chem Biol. 2015;11(9):625–31. PMCID: PMC5714517
- 1.Donia M. A Toolbox for Microbiome Engineering. Cell Syst. 2015;1(1):21–3. PMID: 27135687
- 1.Donia M, Fischbach M. HUMAN MICROBIOTA. Small molecules from the human microbiota. Science. 2015;349(6246):1254766. PMCID: PMC4641445
- 1.Donia M, Cimermancic P, Schulze C, Brown L, Martin J, Mitreva M, Clardy J, Linington R, Fischbach M. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell. 2014;158(6):1402–1414. PMCID: PMC4164201
- 1.Williams B, Van Benschoten A, Cimermancic P, Donia M, Zimmermann M, Taketani M, Ishihara A, Kashyap P, Fraser J, Fischbach M. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014;16(4):495–503. PMCID: PMC4260654
- 1.Kwan J, Tianero M, Donia M, Wyche T, Bugni T, Schmidt E. Host control of symbiont natural product chemistry in cryptic populations of the tunicate Lissoclinum patella. PLoS One. 2014;9(5):e95850. PMCID: PMC4008419
Research Area