2023 marks the fifth year of the NIH-funded New Jersey Alliance for Clinical and Translational Science (NJ ACTS) TL1 fellowship program. Two of this year’s Fellows, graduate student Sophia Koval and postdoc Devin Simpkins, hail from the Princeton University Department of Molecular Biology (MOL), which has also hosted several prior fellowship recipients.

In keeping with the mission of the National Center for Advancing Translational Sciences (NCATS)—to advance the process of turning research observations in the laboratory, clinic, and community into interventions that improve health—NJ ACTS is continuing its commitment to training the next generation of translational scientists. The NJ ACTS TL1 fellowship program makes awards to young scientists at participating research institutions, which include Princeton University, Rutgers University, and the New Jersey Institute of Technology. Accepted fellows receive special training in topics relevant to translational team research across disciplines, such as fostering collaboration with clinical and industry partners, scientific communications, grant writing, and organizing clinical trials. They also receive a stipend and funding for training and research-related expenses. This support is aimed at supplying predoctoral and postdoctoral researchers with the skills to shepherd their advances in the lab into interventions helping patients in the clinic.

As part of their appointments, fellows also gain access to resources that their home institution may not have. For Koval and Simpkins, the program provides access to a network of mentors with extensive clinical expertise from Rutgers and other institutions who can advise them on how to tailor their work for success in a translational setting.

Coincidentally, both Koval and Simpkins are pursuing research projects aimed at gaining a better understanding of how the gut microbiome—the community of microbes that colonizes the human gut—affects human health. It’s estimated that there are as many as a thousand different species of bacteria that call the human gut home, many of which are critical to the proper function of bodily systems. For example, some gut bacteria help with digestion by breaking down compounds that human cells can’t. Others in the gut community are capable of inciting or suppressing immune reactivity and therefore have outsize impacts on the human immune system.

“These communities of bacteria are both individualized and dynamic; everyone's is unique and can change over time based on environment, diet, age, medicine use, and many other factors,” says Koval.

Koval thinks this variability could explain some of the of half-million adverse reactions to orally delivered pharmaceuticals that occur annually in the US that are not otherwise linked to misuse of the drug or to genetic differences in the people who take them.

“Some bacteria have the ability to chemically alter drugs. Sometimes when that happens, bacteria end up transforming a drug into a different compound that does not work the same way the original drug does,” she explains.

Working under the supervision of MOL professor Mohamed Donia, Koval has developed a system to study whether and how a person’s gut bacteria modify pharmaceutical compounds. Knowledge gleaned from these studies could be used to predict how people with different microbiome compositions might react to those drugs.

“Sophia’s project is truly translational, with direct implications for personalized medicine and clinical practice. By critically complementing her basic science training at Princeton, the NJ ACTS award will provide Sophia with the clinical training, programming, and resources necessary to fully translate her research findings,” says Donia.

Meanwhile, Simpkins, who is working in the laboratory of MOL assistant professor and Pew scholar John Brooks, is also investigating how gut bacteria interact with their human hosts. She is pursuing the surprising observation that certain bacteria in the gut are responsive to circadian rhythms, 24-hour cyclic processes that occur in response to signals such as ambient light. One bodily system particularly sensitive to circadian rhythms is the immune system, whose activity waxes and wanes at different times of day.

“The bacteria in your gut also change across the 24-hour cycle and along the length of the digestive system,” notes Simpkins. “We are interested in how circadian changes and localization of the microbiome affect immunity of the host.”

“Although research within the microbiome has occurred over the past several decades, we still do not understand how members of the microbiome are spatially localized within the gastrointestinal tract. Devin’s work seeks to determine how the microbiome is organized in time and space,” says Brooks.

Knowing where a bacterial species is found, and when, could help inform physicians about what time of day a patient should take a certain probiotic to repopulate the gut with beneficial species after a course of antibiotics. Simpkins also points out that circadian-governed changes in members of the gut bacterial community could affect what nutrients or chemicals they produce. This can then have knock-on effects on immunity or any number of other body systems, so as part of her work she plans to examine whether circadian rhythms affect levels of various bacterial by-products.

The sheer complexity of the gut microbiome has historically made it difficult to study, but recent technological advances now enable researchers to pursue hypotheses at unprecedented depth by allowing them to study thousands of samples simultaneously. Princeton is well equipped for these studies, with several prominent laboratories using state-of-the-art instrumentation and developing new ways to employ and improve emerging technologies.

“The training available to fellows is part of a larger biomedical educational alliance with Rutgers, which also includes an MD/PhD program and opportunities for students to participate in clinical research,” says Dr. Dan Notterman, Princeton’s Co-Director of the NJ ACTS fellowship program.

Graduate students and postdocs are urged to visit the NJ ACTS TL1 fellowship program website to see whether their work might benefit from the program. Anyone from Princeton is welcome to contact the on-campus program manager, Bianca Freda, for more information.

Funding: NJ ACTS is currently supported by Clinical and Translational Science Award grants (UL1TR003017, KL2TR003018 and TL1TR003019) from the National Center for Advancing Translational Sciences at the National Institutes of Health.