New ideas in the natural sciences
The fund supports the exploration of new concepts that require additional study or experiments before they are ready to become the basis of a competitive proposal to a funding agency.
Finding novel antimicrobials by studying marsupials
Ricardo Mallarino, assistant professor of molecular biology, will study the naturally occurring antimicrobial agents that marsupials — which carry their offspring to term in an external pouch — employ to kill toxic microbes. Marsupials are born without a working immune system and rely for survival entirely on factors secreted by glands found in the pouch or transferred through maternal milk. The researchers will explore the genetic sequences of these molecules, known as antimicrobial peptides, to discover how the genes have evolved over time in ways that contribute to their efficacy against microbes, with the eventual goal of understanding natural defense mechanisms and informing the design of new antimicrobial drugs.
Boosting the ability to study molecules in motion
Amit Singer, professor of mathematics and the Program in Applied and Computational Mathematics, and Charles Fefferman, the Herbert E. Jones, Jr. '43 University Professor of Mathematics, will develop algorithms to enhance the capability of a powerful microscope to capture images of protein structures as they move and change shape. The team will adapt mathematical approaches for use with cryogenic electron microscopy (cryo-EM) to take pictures of not just fixed molecules but also ones that are flexing and morphing into differing shapes, as happens for example when a drug molecule interacts with its target receptor.
Lowering barriers to gene therapy for the brain
Lisa Boulanger, associate professor of neuroscience, will conduct research to improve the safety and efficacy of viruses that are used for gene therapy to treat nervous system disorders including spinal motor atrophy and certain kinds of blindness. The most commonly used viruses are forms of adeno-associated virus, or AAV, in which the viral genes were removed and replaced with therapeutic genes. Boulanger found that these viruses can unexpectedly change the structure of circuits in the brain, changes that are associated with increased exploratory behavior in mice. She and her team will determine how AAV alters neural circuits, screen for approaches to prevent these changes, and facilitate gene therapy in the nervous system.