Mining the human gut microbial microproteome for modulators of inflammation

The human microbiome, the bacteria and other microbes that live in and on us, is inextricably interwoven with our health. While these helpful microorganisms were underappreciated for many years, scientists are recently uncovering new links between our microbial selves and a number of diseases and disorders. It’s clear that our immune systems are tightly tuned into the microbiome, but the exact signals that carry that crosstalk from bacteria to human cells are still largely a mystery. Ami Bhatt, M.D., Ph.D., Michael Bassik, Ph.D., and Livnat Jerby, Ph.D., are leading a project to look at the role of the gut microbiome’s micropeptides, tiny proteins that are themselves poorly understood, in human immune health and disease. They will look specifically at how thousands of different microbial micropeptides act on two types of immune cells, macrophages and dendritic cells, both types known to interact with microbiome bacteria as well as harmful bacteria. Their work could lead to new ways of understanding many human diseases, including autoimmune disease, heart disease and cancer. 

Affiliated Investigators

Ami Bhatt, M.D., Ph.D.

Stanford University

Ami Bhatt is an Associate Professor at Stanford University in the Departments of Medicine (Hematology; Blood & Marrow Transplantation) and Genetics. A physician scientist with a strong interest in microbial genomics and metagenomics, she received her M.D. and Ph.D. from the University of California, San Francisco. She then carried out her residency and fellowship training at Harvard’s Brigham and Women’s Hospital and Dana-Farber Cancer Institute, and served as Chief Medical Resident from 2010-2011. She joined the faculty at Stanford University in 2014 after completing a post-doctoral fellowship focused on genomics at the Broad Institute of Harvard and MIT. 

Prof. Bhatt has received multiple awards including the Chen Award of Excellence from the Human Genome Organisation (HUGO) and the Sloan Foundation Fellowship; she is also an elected member of the American Society of Clinical Investigation. Her team’s research program seeks to illuminate the interplay between the microbial environment and host/clinical factors in human diseases. Her translational laboratory develops and applies novel molecular and computational tools to study strain level dynamics of the microbiome, to understand how microbial genomes change over time and predict the functional output of microbiomes. These innovations facilitate much improved (1) measurement of the types and functions of microbes in patients with non-communicable diseases, (2) understanding of the interactions between microbial genes, gene products, and host cells and (3) testing of the impact of microbially targeted interventions in clinical trials. She is keenly interested to understand how microbes “talk” to one another and to host cells, and to leverage this understanding to improve health and treat diseases. She has also worked collaboratively to mine microbial enzymes from mobile genetic elements and develop these as genome editing/engineering tools. 

In addition to carrying out research at Stanford University, Prof. Bhatt has active collaborations world-wide including in Nigeria and South Africa. She is committed to ensuring that advances in research touch the lives of individuals in all income settings – and thus, in her spare time, enjoys volunteering for the nonprofit she co-founded, Global Oncology and serves as the Director for Global Oncology for Stanford’s Center for Innovation in Global Health.

Michael Bassik, Ph.D.

Stanford University

Michael Bassik is an Associate Professor in the Department of Genetics at Stanford University.  He performed his Ph.D work in Stanley Korsmeyer’s lab at Harvard, exploring the role of BCL-2 family proteins in regulating cell death.  As a postdoc in Jonathan Weissman’s lab at UCSF, he helped develop new high-coverage shRNA screening libraries and mammalian genetic interaction maps, applying these to study the biology of retrograde toxins.  His laboratory at Stanford focuses on development of CRISPR/Cas9 based systems for high-throughput screening by mutagenesis, single and pairwise gene perturbation, and application of these technologies to (1) study mechanisms of cellular uptake by endocytosis and phagocytosis and (2) identify novel drug target combinations for cancer.

Livnat Jerby, Ph.D.

Stanford University

Livnat Jerby is an Assistant Professor in the Department of Genetics at Stanford University. Her research focuses on multicellular circuits as a disease driver and therapeutic avenue, aiming to develop tissue remodeling and immunomodulating interventions for disease treatment and prevention. As a postdoctoral fellow in Aviv Regev's lab at the Broad Institute of MIT and Harvard, she identified novel regulators of T cell exclusion and dysfunction. Her work identified new mechanisms controlling cellular and tissue immunogenicity and demonstrated the potential of epigenetic reprogramming as a therapeutic modality to overcome immunotherapy resistance in cancer. Dr. Jerby holds a B.Sc. in Computer Science and Biology and obtained her Ph.D. in 2016 from Tel Aviv University, where she worked with Prof. Eytan Ruppin, studying non-linear genetic interactions. In November 2020 she joined Stanford Genetics to establish her own lab. Bringing together latest advances in single-cell genomics, imaging, genetic engineering, and machine learning, her laboratory develops scalable systems to study and reprogram multicellular circuits at greater scale, resolution, and depth. Her research has been generously supported by the Rothschild Foundation, the Schmidt Family Foundation, the Cancer Research Institute (CRI), the Burroughs Wellcome Fund (BWF), and Chan Zuckerberg Biohub initiative.