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Mashruwala Lab

Our lab seeks to uncover the molecular underpinnings of bacterial collective behaviors, focusing on space- and time-distinctive cell death.

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Research Summary

What mechanisms underpin bacterial collective behaviors like regulated cell death?

Research Areas

Genetics and Genomics, Molecular and Cell Biology, Microbiology, Bacterial Community Development, Bacterial collective behaviors

Organisms

Bacteria

Bacteria are the amazing architects of life on Earth and impinge on all aspects of our lives. Their roles range from producing oxygen during the Great Oxidation Event and giving rise to our aerobic world, to influencing the course of human development and health. This influence on our bodies is seen through the beneficial role bacteria play in our microbiota, the body’s collection of microorganisms, and in their potential to also act as pathogens that cause infections. Key to bacteria accomplishing these feats is their capacity to assemble into multicellular communities. Yet, our insight into bacterial societies is surprisingly limited, informed by just a handful of model bacterial group traits. The Mashruwala lab seeks to uncover and study bacterial biology, distinct to their life while residing in collectives, and how these behaviors help bacteria shape the world around us and influence the course of human health.

Central to the lab’s focus is understanding the molecular underpinnings of regulated cell death (RCD) in bacteria — a wholly new bacterial group behavior that Mashruwala recently discovered as a postdoctoral researcher at Princeton University.  Bacterial RCD occurs in “societies” formed by Vibrio cholerae, the human pathogen responsible for the cholera disease, and is carried out in precise spatial and temporal patterns that remarkably echo programmed cell death seen in multicellular organisms. By unraveling how bacteria orchestrate this evolutionarily ancient behavior, the Mashruwala Lab aims to reveal pivotal new biology in bacteria, leverage these findings to pioneer innovative therapeutics to curb bacterial infections, and find clues to help us better understand cell death in humans.

The lab applies an interdisciplinary strategy towards solving our research questions. We combine state-of-the-art imaging technologies and genetic perturbations, along with molecular techniques, phenotypic analyses, and automation. This approach fosters discoveries in bacterial biology, and helps us solve underlying molecular mechanisms. The Mashruawala group seeks to be bound by nothing but our creativity, driving us to engineer new approaches and technologies as needed to answer our most pressing research questions.

Principal Investigator

Ameya Mashruwala

Assistant Investigator

Stowers Institute for Medical Research

Lab Philosophy

We embrace a philosophy that intertwines the thrill of discovery with a commitment to excellent science that is both rigorous and done in a safe manner. We believe in the power of curiosity to act as our compass, propelling us forward and driving our scientific endeavors. We view science as an adventure – a journey where it is just as important to learn from what does not work, as it is to celebrate success. Above all, our lab is a space where we have fun and stay safe. We believe that the best scientific achievements come from a team that not only loves what they do but that also upholds high standards of integrity and safety. By always striving to balance fun and rigor in our science, our lab seeks to be a place that is nurturing and that fosters creativity, collaboration, and outstanding scientific contributions.

Why bacteria?

V. cholerae colony undergoing regulated cell death. Brightest areas indicate the highest cell death.

In the Mashruwala Lab, the bacteria responsible for causing the cholera disease, Vibrio cholerae, is at the forefront of our research. This choice is driven by a rare blend of attributes that make V. cholerae an ideal research organism. Specifically, V. cholerae boasts a simple genome, grows rapidly, and performs natural transformation - which is the ability to take up external DNA into the cell and then integrate this on its genome. Additionally, V. cholerae has a dual lifestyle, fluctuating between marine environments and humans. Thus, this organism is highly suited for sophisticated genetic studies and offers a rich biological landscape where we can explore questions regarding both bacterial biology as well as host-microbe interactions.

Our research

V. cholerae colony exhibiting sector formation. Sectors contain variant genotypes that can resist cell death.

Leveraging the unique qualities of V. cholerae, the lab’s research explores the intricate dynamics within bacterial communities. We are fascinated by the specialized biology that bacteria exhibit when in a social setting, while living and interacting with each other or with different bacteria. Bacterial communities can display complex behaviors resembling higher life forms, such as humans. For instance, cells in bacterial assemblages engage in ion channel-dependent cell-cell signaling and nutrient sharing, reminiscent of mechanisms in human tissues. Moreover, they exhibit the formation of complex developmental phenotypes, including a cell death program that is carried out in precise patterns in space and time. Beyond this basic biology, the ability to assemble into communities is key for V. cholerae to cause infection. Thus, studying V. cholerae communal behaviors allows us to learn about fundamental biological processes, bacterial pathogenesis mechanisms, and unlock insights into similar processes in the human body.

Featured Publications

Quorum-sensing- and type VI secretion-mediated spatiotemporal cell death drives genetic diversity in Vibrio cholerae

Mashruwala, A. A., Qin, B., & Bassler, B. L. Cell. 2022 Oct 13;185(21):3966-3979.e13

Cell position fates and collective fountain flow in bacterial biofilms revealed by light-sheet microscopy

Qin, B., Fei, C., Bridges, A. A., Mashruwala, A. A., Stone, H. A., Wingreen, N. S., and Bassler, B. L. 2020. Science, 369(6499), 71–77.

Staphylococcus aureus SufT: an essential iron-sulphur cluster assembly factor in cells experiencing a high-demand for lipoic acid.

Mashruwala, A. A., Roberts, C. A., Bhatt, S., May, K. L., Carroll, R. K., Shaw, L. N., and Boyd, J. M. (2016). Molecular Microbiology, 102(6), 1099–1119.

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