Pew Alumni Forge Partnerships to Spark Novel Scientific Endeavors

When scientists from different backgrounds and viewpoints combine their knowledge, cutting-edge discoveries often result. The Pew Charitable Trusts launched the Innovation Fund last year to fuel interdisciplinary projects involving alumni of Pew’s biomedical scholars, Latin American fellows, and Pew-Stewart Scholars for Cancer Research programs. The 2018 awardees are bringing their unique perspectives and expertise to collaborative research projects that aim to address some of the most challenging questions in human biology and disease and that would be difficult to pursue within a single scientific discipline.

Since 1985, Pew has invested in nearly 1,000 biomedical researchers in the United States and Latin America through its programs, including convening current members and alumni at annual meetings and reunions. These events provide a diverse group of investigators the opportunities to connect and generate ideas for collaborative work. The Innovation Fund leverages this growing community to promote interdisciplinary partnerships in pursuit of solutions to the most pressing problems in biomedicine, and this year’s six teams of investigators are pursuing topics that span the fields of neuroscience, immunology, metabolism, and microbiology.

The 2018 Innovation Fund investigators are:

Andrés D. Klein, Ph.D., and Patricio Olguín, Ph.D.—The genetics of Parkinson’s disease variability

Parkinson’s is not a single disease, but rather a highly variable disorder in which the severity of patients’ symptoms and their life expectancies can differ. Former Pew Latin American fellows Andrés Klein, a geneticist who develops strategies to identify genes and biomarkers of metabolic diseases, and Patricio Olguín, who uses flies as a model organism to study the genetic bases of neurological disorders, are collaborating on a project to uncover the genetic differences that cause the wide spectrum of symptoms seen in Parkinson’s disease. Among the factors that may explain the variations among Parkinson’s patients are modifier genes, which influence the expression of other genes. In their joint venture, Klein and Olguín will probe the network of modifier genes in a fly model of Parkinson’s to help explain the range in symptoms between patients. Their work could identify new targets and aid in the development of personalized therapies for this debilitating disease.

Aaron D. Gitler, Ph.D., and Michael P. Rape, Ph.D.—Novel strategies to study abnormal protein structures in ALS

Pew scholars Aaron Gitler and Michael Rape will combine their respective expertise in neuroscience and biochemistry to design therapies for the fatal motor neuron disease amyotrophic lateral sclerosis (ALS). Gitler’s work on misfolded proteins in neurological disorders and Rape’s extensive knowledge on the protein degradation process naturally complement one another. Research suggests that toxic buildup of an RNA-binding protein in the cytoplasm of neurons contributes to the development of ALS. This protein is particularly difficult to target because its natural form has essential functions in the nucleus. Gitler and Rape will screen for enzymes that can distinguish between the aggregated toxic form of the protein and its proper functional form. Subsequently, they will identify ways to target the identified aggregates for destruction and halt the buildup of the toxic proteins, which could transform current approaches to treating this challenging disease.

Christine Jacobs-Wagner, Ph.D., and Erol Fikrig, M.D.—The biological relationship between Lyme bacterium and ticks

Christine Jacobs-Wagner and Erol Fikrig, both Pew scholars, are partnering to investigate the intricate relationship between the Lyme disease bacterium Borrelia burgdorferi and the insect that carries it: the tick. They hypothesize that a component of the B. burgdorferi cell envelope influences the ability of ticks to tolerate the bacteria and pass them to animals. This team will combine Jacobs-Wagner’s expertise on bacterial physiology and the genetic tools to study bacteria with Fikrig’s work on the immunological response to insect-borne diseases to identify the bacterial products and the tick genes that are important for the bacteria’s successful colonization in the tick and subsequent transmission to animals. This work could broaden the current understanding of this unique pathogen-host relationship and spur new strategies to combat insect-borne diseases.

Edwin R. Chapman, Ph.D., and Dorit Hanein, Ph.D.—Structure of essential proteins for cellular membrane fusion

Pew scholars Edwin Chapman and Dorit Hanein will work to resolve the structure of cellular machinery that is critical for membrane fusion. This cellular machinery, which comprises several key proteins, plays a key role in the fusion of membrane vesicles containing neurotransmitters to the cell membrane, which results in the release of chemicals that relay signals between neurons. Together, Chapman, who has a well-established record of studying membrane fusion proteins, and Hanein, who brings expertise in structural biology, aim to investigate the remodeling of membrane structures during fusion and analyze individual events during this intricate process. This work could provide insight into the molecular mechanisms that mediate synaptic transmission, and more generally, into how membrane fusion events in eukaryotic cells occur.

Niels Ringstad, Ph.D., and Sharad Ramanathan, Ph.D.—Neural sensing and behavioral responses toward pathogens

Organisms are constantly bombarded with pathogenic threats, and the ability to recognize and avoid these dangers is crucial for survival. However, little is known about how organisms sense infection and then change behavior in response. Two Pew scholars, Niels Ringstad and Sharad Ramanathan, are working together to investigate how the nervous system mediates behavior to avoid dangerous pathogens. Ringstad studies the nervous system using Caenorhabditis elegans, a free-living worm, and has developed a novel method to record neuron activity; Ramanathan is interested in understanding how neural circuits drive certain behavioral decisions. Together, they will use the C. elegans model, along with cutting-edge microscopy and statistical tools, to map how neural circuits are affected by infections. They will also seek to identify the genetic changes that accompany modification in the neural circuits. The importance of interactions between the nervous and immune systems and their impact on human health has become increasingly clear, and results from this project could provide important insights into mechanisms of behavioral change induced by infection.

John F. Rawls, Ph.D., and Steven Farber, Ph.D.—The influence of nutrients and microbes on glucose sensitivity

Pew scholars John Rawls and Steven Farber are teaming up to investigate how dietary nutrients, such as fats, alter the body’s ability to sense glucose in the gut. Rawls, who has done extensive research on host-microbe interactions, and Farber, who studies lipid metabolism, both use zebrafish as a model for their respective work, and they recently demonstrated that a high-fat meal lowers the ability of certain cells in the intestines to sense glucose, a process that is dependent on a particular type of bacteria. Glucose sensing is important for proper metabolic function, particularly the release of insulin from pancreatic beta cells. By conducting novel imaging and genetic studies in zebrafish, Rawls and Farber hope to determine the mechanism by which a high-fat diet interferes with intestinal cells’ ability to sense glucose and identify the intestinal microbes that are involved in the process. This work could offer additional information on the role microbes play in nutrition and provide new strategies to combat metabolic disorders such as diabetes and obesity.

Kara Coleman directs The Pew Charitable Trusts’ biomedical programs, including the biomedical scholars, Pew-Stewart Scholars for Cancer Research, and Latin American fellows programs.