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Research

The Groisman Lab seeks answers to a fundamental biological question: How does an organism know when, where and for long to turn a gene on or off?
We address this question by investigating bacterial species that establish intimate interactions with animal hosts.

All organisms respond to a change in their environment by modifying their behavior. We are interested in identifying the specific signals that denote a given environment, the nature of the sensors that detect such signals, and how the sensors transmit this information to the regulators implementing a response that enables the organism to survive and prosper in the new condition.

We investigate the gastroenteritis- and typhoid fever-causing Salmonella enterica and the gut symbiotic bacteria Escherichia coli and Bacteroides thetaiotaomicron.

We have been examining protein sensors that detect extracellular signals and RNA sensors that monitor cellular metabolites and ions. These investigations led both to the discovery of the first signal transduction systems that sense extracytoplasmic magnesium and ferric iron and to the first mRNAs that respond to cytoplasmic magnesium and ATP.

Our research focuses on understanding:

  • how bacteria integrate multiple signals into a cellular response,
  • the mechanisms by which a given signal elicits distinct responses from co-regulated targets,
  • how bacteria from the gut microbiome compete for resources,
  • the genetic basis for phenotypic differences that distinguish closely related bacterial species, such as a pathogen and a symbiont,
  • the biochemical function of novel proteins and
  • the genetic control of virulence factors.

  • Aimilia Krypotou, PhD

    I became interested in the human microbiota when I realized the important role these microorganisms play in our health. However, we still understand very little about the microbiota on a molecular level. I am interested in understanding how the human diet affects the bacteria that live in our gut. The food we consume provides all the necessary nutrients for the survival of the bacteria but also signals which bacterial genes turn on or off. I study how a regulator of gene expression, the transcription factor Rho from the gut bacterium Bacteroides thetaiotaomicron, senses the abundance of different sugars and controls the ability of this bacterium to survive in the gut. I approach my research as a challenging puzzle that I try to solve using molecular biology, biochemistry, and genetics.

  • Nick Pokorzynski, PhD

    All living cells must shift their metabolic priorities to adapt to changing environments. Intracellular bacterial pathogens, such as Salmonella enterica, face host-mediated starvation for essential nutrients, which hinders bacterial growth. Nutritional starvation can also act as a signal to induce virulence programs, further suppressing growth. How do bacteria alter their metabolism to survive hostile growth conditions while still maintaining effective virulence strategies? I am interested in understanding how pathogens shift their metabolic priorities during nutrient starvation and how this growth strategy impacts bacterial virulence inside host cells. By treating central metabolic functions as part of the successful adaptation of a pathogen to nutritional stress, I hope to uncover novel determinants of virulence.

  • Weiwei Han

    I’m fascinated by communities of microorganisms that normally live in harmony with their hosts (aka microbiota). I’m interested in discovering genetic and molecular strategies that specific microbes have evolved to thrive in such complex environments. My current research focuses on a group of bacteria named Bacteroides that are dominant in the human gut microbiota. They are very different and phylogenetically distant from well studied bacteria like E. coli and many pathogens. My work aims to characterize specific mechanisms of gene regulation that are unique to these bacteria and important for gut colonization. Our work has demonstrated that simply having the “right” genes is not enough to succeed; the “right” genetic regulation is key. Our related publications include:

  • Carissa Chan

    Within cells of all life forms - prokaryotic, eukaryotic, and archaeal – proteins carry out the vast majority of biological processes. Each protein has its own biochemical function that contributes to the normal workings of the cell. However, when the cell encounters a new environment, these proteins can undergo substantial adjustments to fulfill new roles that allow the cell to thrive in this new environment. My research focuses on how and why certain proteins are repurposed when bacterial cells are deprived of magnesium. (This condition is experienced when pathogenic bacteria like Salmonella infect host immune cells.) Using genetic and biochemical tools, we are learning that protein repurposing occurs via many mechanisms, such as by changing binding partners, adjusting the rate of protein synthesis and degradation, and diverting scarce resources away from less important and toward more important processes. Repurposing proteins that are already present enables the cell to adapt to new environments rapidly and efficiently. Our work helps us understand how bacteria overcome obstacles like immune defenses and antibiotics.


    I previously trained as a postbaccalaureate fellow at the National Institutes of Health, where I worked in bacterial genetics and cell biology. I strive to be bold and open-minded in my approach to science. At Yale, I am a Gruber Science Fellow and Medical Research Program Scholar. In addition to w

  • Nicole Place

    The microbiome field has acknowledged the importance of good microbes for human health, but we still don’t fully understand the signals in the gut that allow commensal bacteria to proliferate. The gut is a complex ecosystem, and it is expected that these colonization factors are regulated in response to environmental changes, such as diet. If we better understand the regulation of colonization factors in a commensal bacterium like Bacteroides thetaiotaomicron, then we can better establish and maintain commensal bacteria in our microbiomes. While most of my experience has been in molecular biology and genetics (with a focus on DNA and RNA), I joined the Groisman lab to grow my protein-based technique repertoire and to receive training in classical bacterial genetics. As a graduate student at Yale, I was awarded the National Science Foundation Graduate Research Fellowship.

  • Magalí Scocozza

    Bacteroides thetaiotaomicronis a beneficial gut bacterium that accesses nutrients ingested by its mammalian hosts. Interestingly, there are long periods of time when the host organism does not eat. Recent findings in the Groisman lab have shown how carbon starvation triggers properties in B. thetaiotaomicron that are beneficial for its fitness in the gut. Carbon starvation promotes the formation of droplets in B. thetaiotaomicron that results in a biophysical transition leading to the regulation of molecular actuators via selectivity, concentration, and localization. My research focuses on understanding how B. thetaiotaomicron regulates phase separation, in coordination with various processes promoting gut bacterial fitness during carbon starvation. By combining my background in biophysical chemistry with molecular biology, biochemistry, and genetics, I aim to determine how gene regulation mechanisms as well as the physical state of biomolecules help an organism adapt to environmental changes.

    Image: Bacteroides thetaiotaomicron under carbon starvation.

  • Keiichiro Mukai

    Proteins perform the most important functions in all living cells. In pathogenic bacteria, which must successfully adapt to environmental changes within hosts to achieve infection, proteins must be produced at the correct locales, for the right duration, and in the appropriate quantities. While protein synthesis in pathogenic bacteria is well understood, the regulation of protein degradation remains largely unexplored. Proteolysis is an irreversible process that must be tightly controlled. My research focuses on the human gastroenteritis- and murine typhoid-causing Salmonella enterica serovar Typhimurium to understand how pathogens control proteolysis and virulence via proteases and adaptor molecules. This work will reveal novel strategies used by Enterobacteriaceae to cause infection as well as enhance our understanding of proteolytic systems common in all organisms.

    Image: The regulation of protein degradation in the pathogen Salmonella enterica serovar Typhimurium.

  • Pengrui (Pray) Miao

    The human gastrointestinal tract harbors a dense and diverse microbial community that plays crucial roles in human health. It is therefore essential to understand the mechanisms by which commensal bacteria survive and persist in the gut. The Groisman Lab has shown that commensal species Bacteroides thetaiotaomicron employs many molecular mechanisms to promote fitness in the murine gut, including the production of an alternative translation factor to save energy during protein synthesis under carbon starvation. Notably, the genetic interactions between these gut colonization factors and other genes remain unexplored. With my background in bacterial genetics, molecular biology, and biochemistry, I aim to identify these additional genes and elucidate their roles in the regulation of colonization factors.

    Image: The regulation of gut colonization factors in Bacteroides thetaiotaomicron.

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