Research
Research Focus
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.
Research Projects
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.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.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.
Sebin Kang
In bacterial cells, the outer membrane cells plays a crucial role in protection from antibiotics and harsh environments. The outer membrane consists of various proteins, including lipoproteins such as lipopolysaccharide (LPS). The LPS has a dynamic structure that changes through gene regulation in response to targeted antibiotics and is stabilized largely by the divalent ion Mg2+. In the intracellular pathogen Salmonella enterica serovar Typhimurium, the two-component system PhoQ/PhoP responds to low Mg2+ conditions by modifying the phospholipid biosynthesis pathway and thus lipid A composition. My research examines how bacteria carry out and benefit from such modifications in response to nutritional stress during host infection.
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.