Marco Jost

Marco Jost

Assistant Professor of Microbiology
Harvard Medical School
Marco Jost headshot

Marco grew up in Germany and studied biochemistry at the University of Tübingen, where he completed his diploma thesis with Thilo Stehle solving crystal structures of fungal prenyltransferases. He received his Ph.D. in Biological Chemistry from MIT, working with Cathy Drennan to study the roles of coenzyme B12 in photosensing and radical catalysis, and did post-doc work with Jonathan Weissman and Carol Gross at UCSF, where he developed CRISPR screening methods and used them to identify the molecular target of an anti-cancer drug and to probe glycolipid signaling at the host-microbiome interface. 

Research Interests

The overarching goal of the Jost lab is to define molecular mechanisms of host-microbiome communication using a combination of systematic CRISPR technologies, physiological cell models such as organoids, and targeted approaches from microbiology, immunology, and chemical biology.

Microbiome biology is fascinating. Sweeping efforts over the past decades have provided a catalog of the microbes in the human microbiome – we know who’s there – and revealed a staggering extent of communication between these microbes and the human host: these microbes are essential for immune system development, impact how much we eat and how many calories we extract, and change our behavior. This communication is a fundamental aspect of human biology and dysregulation can trigger diseases in every organ.

At the same time, we largely lack an understanding of the mechanisms underlying this communication: which microbes cause these phenomena? What molecules do they produce to do so and which receptors do these molecules bind? How does such binding change immune responses or the rate of fat burning or the activities of neurons? And what happens when communication goes awry? The advent of CRISPR technologies has provided tools to begin answering these questions: we can probe, rapidly and at large scale, how deletion, overexpression, or mutation of genes in both microbes and human cells changes a given phenotype. Such systematic and reciprocal genetic approaches are ideally suited to connect specific species and molecules to host pathways – to define the language of communication. 

We are interested in probing, for example, how recognition of chemical structures on microbial surfaces allows immune cells to discriminate microbes and mount specific responses, how human cells parse the complex repertoire of molecules from the microbiome, and how gut microbes affect systemic processes by interfacing with endocrine cells in the gut epithelium. The resulting mechanistic insight will be essential for the development of therapeutics for microbiome-associated diseases and more broadly, given how fundamentally the microbiome affects human physiology, such investigations are likely to uncover exciting basic biology.

Selected Publications

  1. Jost M*#, Jacobson AN*, Hussmann JA, Cirolia G, Fischbach MA#, Weissman JS#. CRISPR-based functional genomics in human dendritic cells. eLife, 2021, 10, e65856.
    * contributed equally; # corresponding author.
  2. Jost M*, Santos DA*, Saunders RA, Horlbeck MA, Hawkins JS, Scaria SM, Norman TM, Hussmann JA, Liem CR, Gross CA, Weissman JS. Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs. Nature Biotech 2020, 38, 355-364. 
    * contributed equally.
  3. Jost M*, Weissman JS*. CRISPR approaches to small molecule target identification. ACS Chem Bio 2018, 13, 366-375. * corresponding author
  4. Jost M, Chen Y, Gilbert LA, Horlbeck MA, Krenning L, Menchon G, Rai A, Cho MY, Stern JJ, Prota AE, Kampmann M, Akhmanova A, Steinmetz MO, Tanenbaum ME, Weissman JS. Combined CRISPRi/a-Based Chemical Genetic Screens Reveal that Rigosertib Is a Microtubule-Destabilizing Agent. Mol Cell 2017, 68, 210-223. 
  5. Jost M, Fernández-Zapata J, Polanco MC, Ortiz-Guerrero JM, Chen PY, Kang G, Padmanabhan S, Elías-Arnanz M, Drennan CL. Structural Basis for Gene Regulation by a B12-Dependent Photoreceptor. Nature 2015, 526, 536-541.
  6. Jost M, Cracan V, Hubbard PA, Banerjee R, Drennan CL. Visualization of a Radical B12 Enzyme with its G-protein Chaperone. PNAS 2015, 112, 2419-2424.

Selected Awards

2019–2021  NIH K99 Pathway to Independence Award
2018–2019  UCSF PBBR Postdoctoral Independent Research Grant
2015–2018 NIH NRSA Individual Postdoctoral Fellowship
2014 MIT Department of Chemistry Award for Continued Excellence in Teaching
2013 Delegate to the 63rd Meeting of Nobel Laureates in Lindau, Germany 
2013 International Centre for Diffraction Data Ludo Frevel Crystallography Scholarship 
2012–2013 MIT Poitras Pre-Doctoral Fellowship
2011 MIT Department of Chemistry Award for Outstanding Teaching