Nine Harvard faculty members are among 47 scientists nationally whose promising and innovative work was recognized Monday (Sept. 22) with the announcement of two grant programs through the National Institutes of Health (NIH).
The grants, expected to total $138 million over five years for all recipients, recognize established researchers through the Pioneer Award and young scientists through the New Innovator Award.
The awards support potentially high-impact research whose approaches have the potential to transform biomedical and behavioral science.
“Nothing is more important to me than stimulating and sustaining deep innovation, especially for early career investigators and despite challenging budgetary times,” said NIH Director Elias A. Zerhouni. “These highly creative researchers are tackling important scientific challenges with bold ideas and inventive technologies that promise to break through barriers and radically shift our understanding.”
Zerhouni said the programs are central to NIH’s efforts to encourage novel investigator-initiated research and to support more investigators early in their careers.
Pioneer Awards provide $2.5 million in direct costs to established investigators over five years. The New Innovator Awards provide $1.5 million for direct costs over five years to researchers who have not received an NIH regular research grant in the past.
Harvard faculty members who won Pioneer Awards are:
• Charles M. Lieber, the Mark Hyman Jr. Professor of Chemistry in the Faculty of Arts and Sciences, will develop interfaces between nanoelectronic devices and cells to create new biomaterials and tools for studying the brain. His group’s initial focus under its Pioneer Award will be on developing new nanoscale electrophysiology tools for measurement of electrical and biochemical signaling in brain tissue and cultured neural networks. These nanoelectronic tools could help in understanding the behavior of cellular networks. Lieber also aims to develop sophisticated cell/tissue interfaces for prosthetics and other medical devices, and to create two- and three-dimensional functional biomaterials capable of processing electronic and biochemical signals.
• Tom Maniatis, the Jeremy R. Knowles Professor of Molecular and Cellular Biology in the Faculty of Arts and Sciences, studies the basic mechanisms of gene regulation in the brain. His Pioneer Award will support research using stem cells in conjunction with the tools of molecular and cellular biology to examine the genesis of Lou Gehrig’s disease, also known as amyotrophic lateral sclerosis (ALS). Little is known about the causes of this neurodegenerative disease that affects motor neurons. New techniques make it possible to use ordinary skin cells from patients to generate stem cells that can, in turn, give rise to motor neurons. Maniatis and colleagues plan to study patient-derived motor neurons in cultures to gain insights into the origins of ALS, which may lead to the development of new drugs to treat this incurable disease.
• Hongkun Park, professor of chemistry and of physics in the Faculty of Arts and Sciences, will develop new nano- and microelectronic tools to study the design principles of the brain. Neuronal networks — collections of neurons interconnected by synaptic junctions — form the physical basis of our brains. Over the years, neuroscientists have learned a lot about individual neurons and have studied whole brains using MRI and other imaging techniques. However, the relationship between connectivity among multitudes of neurons and brain function is poorly understood. Park will develop tools that can perturb and record each and every neuron in a slice of functioning brain simultaneously, in real time. These tools will enable scientists to investigate how synaptic connectivity translates to network function, helping to unravel the design principles of the brain. These tools will also allow cell network-based diagnostics of neurodegenerative diseases.
• Aravinthan D.T. Samuel, associate professor of physics in the Faculty of Arts and Sciences, will develop new biophysical and imaging techniques to understand the neural basis of behavior in fruit fly, or Drosophila, larvae. The project reflects Samuel’s longstanding interest in the molecular and cellular underpinnings of purposeful behavior, dating back to his studies as a Harvard undergraduate and graduate student —with biophysicist Howard C. Berg — of how E. coli detects and swims toward food. Samuel’s own lab studies the neural basis of navigational behaviors in the nematode Caenorhabditis elegans. With a brain containing some 3,000 neurons, the fruit fly represents a big step up in complexity. Samuel and his colleagues will examine larval behavior using a biophysical approach, building new microscopes to noninvasively measure neural activity in large numbers of neurons of freely moving larvae as they execute their normal behaviors.
• Ann Hochschild, a professor of microbiology and molecular genetics at Harvard Medical School, will use bacterial systems to study infectious particles called prions, which are behind some of the worst neurodegenerative diseases, including bovine spongiform encephalopathy, known as “mad cow disease,” and its human equivalent, Creutzfeldt-Jakob disease. The ailments are caused when the prion protein goes awry, initiating the formation of self-propagating aggregates within the brain, and causing a fatal collapse of neurological capabilities. Hochschild will look for prions in bacteria, using an E. coli-based genetic detection system. Since bacterial systems represent cellular life stripped down to the essentials, E. coli would provide a perfect model for studying prion proteins at their most basic level, Hochschild said. “For understanding disease, it’s important to understand the fundamental biology of the system. If prion proteins are found in bacteria, we will undoubtedly learn many relevant things about the underlying biology of prion formation.”
Faculty members receiving New Innovator Awards are:
• William M. Shih, an assistant professor of biological chemistry and molecular pharmacology at Harvard Medical School and the Dana-Farber Cancer Institute, is working to develop tools for atomic-resolution imaging of membrane proteins to enable structure-based drug design.
• Amy J. Wagers, an assistant professor of stem cell and regenerative biology in the cross-School Department of Stem Cell and Regenerative Biology and an assistant professor of pathology at Harvard Medical School and the Joslin Diabetes Center, will study the mechanisms by which aging impairs blood cell function and develop strategies to prevent or reverse these age-acquired defects.
• Sean M. Wu, an instructor in medicine at Harvard Medical School and Massachusetts General Hospital, will employ mechanisms of embryonic development to engineer functional tissues for organ regeneration using pluripotent stem cells from different species.
• Samara Reck-Peterson, an assistant professor of cell biology at Harvard Medical School, has been awarded an NIH New Innovator Award to get under the hood of molecular motors inside cells and to discover how they perform some of their most basic functions. Cells are hardly the viscous blobs of protoplasm we often imagine they are. If anything, they’re more akin to micro-scaled industrial factories jam-packed with workers and machines, operating with mind-boggling efficiency. Central to these processes are molecular machines, tiny motors that do much of the cell’s heavy lifting.
Reck-Peterson will use the fungus Aspergillus as a model organism and focus on two motors called dynein and kinesin, so important that “We would die without them,” according to Reck-Peterson. “But there is still so much we don’t know about them. How do they move? How do they find the right cargo? How do they carry it? How do they get to where they need to go?”