As Partners in Cutting-Edge Biomedical Research, Pew-Supported Scientists Seek Answers

The 16 accomplished scientists in The Pew Charitable Trusts’ 2024 class of Innovation Fund investigators have expertise in microbiology, immunology, bioengineering, and more—and are teaming up to tackle some of the most pressing challenges facing human health.

Collaboration is essential to scientific innovation. Many of the vital treatments, therapies, and vaccines available today have resulted from researchers around the world combining their efforts in pursuit of discovery. In 2017, Pew launched the Innovation Fund to support this type of scientific collaboration among alumni of its biomedical programs in the United States and Latin America.

Combating disease through global protein synthesis

Global protein synthesis, or the rate at which proteins are produced throughout an organism, is vital to nearly all biological functions. Small molecules called ribosomes are responsible for increasing protein production, which can alleviate the effects of certain diseases. However, the underlying mechanisms behind this process have eluded scientists, and there are no pharmacological approaches that leverage protein synthesis.

Maria Barna, Ph.D., of Stanford University, and Christine Dunham, Ph.D., of Emory University, hope to change this. The team seeks to unravel the mechanisms behind the specific compounds that enhance protein production and evaluate their role in diseases such as amyotrophic lateral sclerosis (ALS) and Diamond Blackfan anemia. The pair’s efforts could shed light on the mechanisms driving this process and provide a new pathway for treating disease through ribosome reprogramming.

Unraveling interactions between immune cells and the gut

The digestive tract is home to a constellation of microbes known as the gut microbiome, and research has increasingly shown just how critical this array of organisms is to a person’s well-being. The gut microbiome is responsible for recognizing beneficial microbes and fighting off harmful ones, and it affects everything from mood and weight to energy and immune function.

Ilana Brito, Ph.D., of Cornell University, and Gabriel Victora, Ph.D., of The Rockefeller University, together are examining interactions between gut microbiota and intestinal immune cells. They’ll explore this by way of germinal centers—environments where specific immune cells, called B cells, produce powerful, infection-fighting antibodies. The pair will investigate antibody development and the specific bacterial antigens that generate these antibodies, which can successfully regulate the intestine’s microbial balance. Their work will help identify which bacteria are key players in gastrointestinal disorders when this balance is disrupted.

Transforming insect-borne virus detection

Through the simple act of biting, insects such as mosquitoes and ticks are experts at proliferating disease. Known as arboviruses, these illnesses—which include dengue and chikungunya—pose a public health threat throughout the globe, including in parts of Latin America.

Argentina-based scientists Daiana Capdevila, Ph.D., of Fundación Instituto Leloir, and Ana Peinetti, Ph.D., of Instituto de Química Física de los Materiales, Medio Ambiente y Energía (CONICET-Universidad de Buenos Aires), aim to pioneer an accessible testing method for these diseases. Current diagnostic methods can be costly, time-consuming, and difficult to transport. The researchers will develop an in vitro “on-off switch” platform where engineered molecules capture viral antigens in patient serum samples, triggering a positive or negative readout. Using this approach, they hope to incorporate antigen testing into routine care and improve detection of emerging viruses.

Examining cell functions key to mammalian growth

In mammals, chondrocytes—specialized cells on the ends of bones—swell massively and secrete large proteins that assist with bone growth. How these chondrocytes function in a swollen state, however, is a mystery.

Kimberly Cooper, Ph.D., and Elizabeth Villa, Ph.D., both of the University of California, San Diego, are teaming up to address this question. By combining Cooper’s extensive experience in skeletal biology and Villa’s expertise in structural cell biology, the researchers plan to examine what drives this swelling and protein secretion—creating high-resolution 3D images of biological samples to closely examine chondrocytes and their function. This collaborative work could reveal key insights into the cell functions that are fundamental to the growth of all mammals.

Pioneering approaches to studying protein interactions

Many key cellular processes are carried out by a process known as protein binding. It’s believed that these important protein-protein interactions likely originated through co-evolution. However, this process is often poorly understood because existing approaches have limited scientists to studying only one protein interaction at a time.

K. Christopher Garcia, Ph.D., of Stanford University, and Jesse Bloom, Ph.D., of the Fred Hutch Cancer Center, will develop a method for examining protein-protein interactions and engineering new ones. A new platform created by the Garcia lab has made it possible to examine two proteins at the same time. Combining this technology with the Bloom lab’s expertise in predictive virology, the team will explore protein binding in immunity and apply it to the development of antibodies that are resilient to rapidly mutating diseases such as SARS-CoV-2 and cancer.

Revealing insights into neuronal function

The nervous system is fundamental to how humans navigate the world. Made up of the brain, spinal cord, and nerves, this network governs everything from movement to digestion. Neurons are the building blocks of the nervous system, and their specialized components, called dendrites and axons, help collect information and send signals throughout the body.

Jonathon Howard, Ph.D., of Yale University, and Tomás Falzone, Ph.D., of Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET – MPSP) and Facultad de Medicina, Universidad de Buenos Aires, will combine their unique expertise to uncover the cellular structure behind the sizing of dendrites and axons and how this affects neuronal signals. Together, their efforts could unveil new findings about neurons, as well as bring forth foundational insights into how these processes can be disrupted in certain neurodegenerative disorders.

Examining immune systems across species

The immune system’s network of organs, white blood cells, proteins, and chemicals work together to fight infection, and a protein structure known as an immunoglobulin (Ig) domain plays a crucial role in the body’s defense mechanism.

Michael Kuhns, Ph.D., of the University of Arizona, and Nels Elde, Ph.D., of the University of Utah, are taking a cross-species approach to examining the ins and outs of Ig domains within CD4 T cells, which are specialized immune cells. The team previously discovered that the Ig domains in CD4 T cells of mammals are different than those in fish, and they believe these distinctions could have broader implications for immune function. They’ll test this through specially engineered models that swap the CD4 Ig domains between mice and fish, an approach that could uncover insights into the immune system at large.

Redefining the link between food and human health

Researchers have long held that certain diet choices are better for health than others, and many people turn to nutrition facts for insight into how specific foods affect their wellbeing. Yet the relationship between food and the human body is far more complex than calories or grams of sugar.

Seth Rakoff-Nahoum, M.D., Ph.D., of Boston Children’s Hospital and Harvard Medical School, and Jing-Ke Weng, Ph.D., of Northeastern University, are combining their efforts to redefine the intricate relationship between food and health. Together, they’ll precisely trace food molecules’ pathways, modifications, and host interactions and explore a person’s immune response to food proteins. Their work could expand current knowledge of food beyond nutritional values to include food-host interactions, with the potential to inform disease prevention and treatment and fundamentally transform approaches to global health.

Ana-Rita Mayol is a project director and Donna Dang is a principal associate with The Pew Charitable Trusts’ biomedical research programs.