- January 10, 2023
Postdoctoral position available in the Groisman lab, Microbial Sciences Institute at Yale University
- August 10, 2022
Dr. Weiwei Han presents Ph.D. thesis
- April 29, 2022Source: YaleNews
Eight Yale Faculty Members Elected to American Academy of Arts and Sciences
- September 20, 2019
Groisman receives mentorship award
- December 17, 2018
Sugar targets gut microbe linked to lean and healthy people
- June 22, 2018
Nine Faculty Members Appointed to Endowed Positions
- October 13, 2016
In creation of cellular protein factories, less is sometimes more
- October 13, 2016
In creation of cellular protein factories, less is sometimes more
Welcome
The Groisman Lab seeks answers to a fundamental biological question: How does an organism know when, where, and for how long to turn a gene on or off? We address this question by investigating bacterial species that establish intimate interactions with animal hosts. Please view our Research, Publications, and News.
The bacterium Salmonella enterica serovar Typhimurium narrows down the spectrum of substrates degraded by the proteases Lon and ClpAP in response to low cytoplasmic Mg2+, a condition that decreases protein synthesis. This control is exerted by PhoP, a transcriptional regulator activated in low cytoplasmic Mg2+ that governs proteostasis and is conserved in enteric bacteria. The uncovered mechanism enables bacteria to control the abundance of preexisting proteins.
Illustrated by Jennifer Aronson
The small proteins MgtU and MgtR regulate Salmonella virulence and growth in low Mg2+ conditions by controlling the stability of the Mg2+ transporters MgtA and MgtB.
FEDS: a Novel Fluorescence-Based High-Throughput Method for Measuring DNA Supercoiling In Vivo.
Map of SupR, a supercoiling reporter plasmid for enterobacteria.
The three core cellular processes (chromosome replication, transcription, and translation) and coregulatory relationships among them.
The BT4338 regulon in bacteria experiencing carbon limitation.
Activator of One Protease Transforms Into Inhibitor of Another in Response to Nutritional Signals.
Acetyl-CoA-promoted acetylation of the HspQ protein increases the specificity of the Lon and ClpAP proteases.
The Expanded Specificity and Physiological Role of a Widespread N-degron Recognin.
Candidate ClpS substrates revealed by proteomics.
Salmonella Expresses Foreign Genes During Infection by Degrading Their Silencer.
Salmonella expresses horizontally transferred genes by degrading their silencer, H-NS. HTGs are transcriptionally repressed by H-NS, which binds to their regulatory regions.
We report that persistent bacteria form as a result of slow growth alone, despite opposite changes in the abundance of proteins, metabolites, and signaling molecules. Our findings argue that transitory disturbances to core activities, which are often linked to cell growth, promote a persister state regardless of the underlying physiological process responsible for the change in growth.
Dietary sugar silences a colonization factor in a mammalian gut symbiont.
Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.
We report that the Salmonella adaptor ClpS binds to the N terminus of the regulatory protein PhoP, resulting in PhoP degradation by ClpAP. The identified mechanism provides a simple means to spare specific substrates from an adaptor-dependent protease.
Metabolic flux controls chondroitin sulfate utilization in Bacteroides thetaiotaomicron.
Free cytoplasmic Mg2+ inhibits Pi starvation response.
A reduction in adaptor amounts creates a hierarchy among substrates delivered to a protease by an adaptor. The ClpAP protease degrades certain substrates directly but requires the adaptor ClpS to degrade others.
Under non‐inducing conditions for the master virulence regulator PhoP (gray), the anti‐virulence protein CigR is expressed independently of PhoP, and the virulence protein MgtC is not expressed (left). At early times under inducing conditions (pink), PhoP promotes expression of MgtC, which, sequestered by CigR, does not inhibit the F1Fo ATP synthase (ATPase) or protect PhoP from degradation (middle). At late times under inducing conditions (blue), MgtC amounts supersede CigR amounts, which result in MgtC binding to and inhibition of the ATPase (right). In addition, MgtC protects PhoP from degradation, thereby increasing PhoP amounts and enabling transcription of a subset of PhoP‐activated genes (right).
Cells' energy and protein synthesis potentials depend on the availability of Mg2+. Bacteria sense and respond to various degrees of Mg2+ limitation. Non-physiological increase in ATP disrupts essential Mg2+-dependent processes. Cell restores free Mg2+ levels by shutting down synthesis of ATP and ribosomes.