Scientists Break New Ground With Creative Partnerships

The Pew Charitable Trusts’ 2023 class of Innovation Fund investigators—12 accomplished scientists with expertise in cancer biology, neuroscience, immunology, and more—are pairing up to explore challenges in human health and medicine.

Collaboration is at the heart of scientific advancement: From engineering innovative cancer therapies to developing new strategies to meet public health crises, scientists achieve breakthroughs when they reach across disciplines to unite for a common cause.

For nearly 40 years, The Pew Charitable Trusts has supported more than 1,000 early-career scientists spearheading high-risk, high-reward research across a variety of disciplines. And in 2017, Pew launched the Innovation Fund to spark scientific collaboration among alumni of its biomedical programs in the United States and Latin America.

Clues about how animals feed their young

Human infants aren’t the only mammals who cry when they’re hungry. Many animals, from mice to birds, rely on vocalizations to alert their parents when it’s time to eat. Songbird chicks chirp special begging calls, while mice produce ultrasonic sounds that signal their hunger. While this communication is fundamental to survival, scientists know little about the neural pathways involved in this process. 

Jesse Goldberg, M.D., Ph.D., from Cornell University, is teaming up with Robert Froemke, Ph.D., of New York University’s Grossman School of Medicine, to better understand how animals respond to their young’s need to feed. The Goldberg and Froemke labs will run parallel studies in birds and mice to learn more about the dopamine and oxytocin signals in the neurons that drive the vocalizations. By exploring this process in two distinct species, the pair hopes to shed light on parent-child interactions at both the neural and behavioral levels.

The biology behind decision-making

From choosing what to wear in the morning to deciding what to eat for lunch, humans are constantly making decisions. But what happens at a neurological level when we change our minds? Despite the thousands of choices people make each day, the biology behind this aspect of decision-making in the brain continues to elude scientists. 

Roozbeh Kiani, M.D., Ph.D., of New York University and Nuo Li, Ph.D., of Baylor College of Medicine, will combine Kiani’s work on the computational principles of decision-making in monkeys with Li’s research on the neural circuits driving learning and memory in mice. The pair plans to develop a framework to model neural responses to pinpoint when these animals are changing their minds. The researchers will then work to identify the parts of the brain and specific mechanisms that influence decision-making, as well as what other factors, such as memories or sensory input, might trigger a decision change.

How plants respond to external stressors

Plant cells rely on organelles called plastids for survival: they’re fundamental to a plant’s metabolism and nutrient production, and they also communicate with the nucleus when faced with external stressors such as extreme heat or disease. While scientists know what happens when the nucleus communicates with the plastid, the signals sent from the plastid to the nucleus are less understood. Deciphering this biology will shed light on how plant biology can be engineered to adapt to climate change.

Patricia Leon Mejia, Ph.D., from Universidad Nacional Autónoma de México, and Luis G. Brieba de Castro, Ph.D., from El Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, are looking into how the nucleus and plastid share information. Recent research has identified a specific protein class that might play a role in communication between the plastid and nucleus. Combining Leon Mejia’s expertise in apocarotenoid proteins and Brieba de Castro’s research in protein folding and biochemistry, the pair will identify the receptors and signaling molecules important to this communication. Understanding the signaling pathway from the plastid to the nucleus will give scientists a clearer picture of how exactly plants react to stress, as well as offer new approaches to improving crop production and yield.

The genetics behind cyanobacteria

The term “cyanobacteria” may be unfamiliar to most people, but chances are you’ve encountered them. These ubiquitous bacteria inhabit a wide range of environments, from ocean ecosystems to desert landscapes. They’re responsible for a majority of Earth’s carbon fixation—when organisms draw out carbon from inorganic molecules for photosynthesis—which produces oxygen as a byproduct.

Katsuhiko Murakami, Ph.D., from Pennsylvania State University, and Gene-Wei Li, Ph.D., from Massachusetts Institute of Technology, will explore the complex genetics of these microorganisms. The pair will look at transcription termination, a key step in cyanobacteria gene regulation that tells the cell when to stop converting genetic information from DNA to RNA (the molecular instructions for producing proteins). While the mechanisms behind transcription termination are well known in other organisms, the inner workings of this process in cyanobacteria are still largely unknown. Drawing on Murakami’s expertise in structural biology and Li’s knowledge of transcription regulation, the two investigators will establish a model for microbial transcriptional termination in cyanobacteria. This work could unveil new scientific approaches used to study cyanobacteria, photosynthesis-promoting plant cells, and other bacterial groups.

The pathology of inflammatory bowel disease

Our intestines are home to hundreds of bacteria species that play a key role in immune system development. But sometimes these helpful bacteria can become harmful. In the case of people with inflammatory bowel disease (IBD), a bacterium alerts the body’s disease-fighting T cells and triggers an inflammatory response characterized by abdominal pain and persistent diarrhea. IBD affects millions of people in the United States, and cases are on the rise in older adults, yet the cause of this autoimmune disorder is largely unknown.

Dan Littman, M.D., Ph.D., from New York University’s Grossman School of Medicine, and Michael Birnbaum, Ph.D., from Massachusetts Institute of Technology, are looking for a root cause. The pair will merge Littman’s work exploring how and why specific bacteria affect T cell development with Birnbaum’s expertise in T cell receptor-antigen binding in an effort to characterize the specific microbes and antigens that drive these harmful responses in the gut. Together, their work could offer new treatment avenues for IBD, such as novel therapies targeting pathogenic microbes or T cells.

The cell components that regulate metal homeostasis 

Many living organisms, including humans, rely on transition metals for good health. These key dietary nutrients, such as iron and zinc, play a critical role in cellular activities like metabolism. But sometimes, our body’s ability to properly acquire, store, and locate these metals is disrupted, which can lead to disease. Getting a clearer picture of how transition metals are processed, and what happens when this goes awry, could help scientists pinpoint new strategies to address a slew of illnesses.

Donita C. Brady, Ph.D., from University of Pennsylvania's Perelman School of Medicine, and Kivanç Birsoy, Ph.D., of The Rockefeller University, are collaborating on research to examine the specific cell components that regulate or respond to transition metals. The team will draw on Brady’s expertise in metallobiology and chemical biology, as well as Birsoy’s research in metabolism and organelle biology, to map metal-protein interactions across cell compartments. Then, the labs will categorize previously unidentified metabolic pathways that adapt to fluctuations in metal availability. Together, their work could offer new knowledge about how cells maintain the delicate balance between metal deficiency and toxicity and ward off disease.

Donna Dang is a principal associate and Kara Coleman is a former project director with The Pew Charitable Trusts’ biomedical programs.