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URMC / Del Monte Institute for Neuroscience / NeURoscience Blog / January 2021 / The perfect pilot: How a grant takes flight

The perfect pilot: How a grant takes flight

Ania Busza, M.D., Ania Majewska, Ph.D., Ed Freedman, Ph.D., Margot Mayer-Proschel, Ph.D., Harris Gelbard, M.D., Ph.D.At the Del Monte Institute for Neuroscience, there is a commitment to support novel, high-risk research that opens new doors of understanding of the brain and central nervous system. Pilot grants are an indispensable tool to support the initial experiments designed to pursue new fields of investigation and generate the data needed to secure external support, publish findings, and share data with scientific colleagues across the globe. Since 2015, philanthropic support for the Institute’s pilot programs has more than tripled to $800,000. Thirteen novel research projects received pilot funding in 2020, almost three times the number from five years ago. In the past five years, more than $2.7 million in pilot funding has generated more than $31 million in external research support.

Other changes have elevated the process so that only highly meritorious projects are awarded these pilots. “We have moved to a highly sophisticated review process, where two thirds of the reviewers come from outside of the University, including world leading experts. It provides an unbiased appraisal and raises the level of excellence required for our pilot grants,” said Ian Dickerson, Ph.D., Del Monte pilot grant program director. “It is run like a National Institutes of Health study section.”

Margot Mayer-Proschel, Ph.D., professor of Biomedical Genetics and Neuroscience, received a $40,000 Schmitt Program in Integrative Neuroscience pilot grant in 2016. This initial support has led to more than a million dollars in funding, and generated data and findings that have resulted in multiple publications and presentations. The recently designated Intellectual and Developmental Disabilities Research Center at the University can also be linked back in part to the award of this pilot. Focusing on in utero brain development, the Mayer-Proschel lab investigated two insults they believed could be an early risk factor for autism – iron deficiency and the genetic mutation 16p11.2. While it had been established that the genetic mutation 16p11.2 is a risk factor for autism, they needed data showing an autism relevant functional consequence in the offspring that was exposed to maternal iron deficiency in utero, so they applied for pilot funding.Embryonic mouse brain stained with antibodies against Nkx2.1 (green) - a critical transcription factor that defines specific brain regions important for the creation of interneurons, cells that play a critical role in establishing the excitatory and inhibitory balance of the brain later in life. “Using a nutrition based animal model, we found such an intriguing set of data, suggesting that iron deficiency alone during the gestational period really changes the balance of excitation and inhibition in neuronal circuits later in life – which is exactly what you would expect in the context of autism,” Mayer-Proschel said. “We didn’t even finish all the experiments that we originally proposed – we incorporated these data immediately into a bigger NIH grant proposal.” In 2018, they received a $1.4 million NIH grant, bolstering the University’s childhood research portfolio. This funding also allowed Mayer-Proschel to recruit new graduate students who continue moving this research forward in several new directions, including the possible implications these insults may play in Alzheimer’s disease. “We got the pilot, we got the grant, and we got the students – and we can keep going on. It literally sometimes just takes a small boost provided by a pilot grant to make bigger steps possible.”

Ed Freedman, Ph.D., associate professor of Neuroscience, has already held multiple presentations, including in Europe, on some of the findings from his 2019 pilot grant. He will apply for federal support to continue research that is using mobile brain/body imaging (MoBI) technology to identify biomarkers in the brain that could be early indicators of Alzheimer’s disease. He and Anton Porsteinsson, M.D., director of the University of Rochester Alzheimer's Disease Care, Research and Education Program, were awarded a $50,000 pilot. As a flagship program of the Del Monte Institute, funds to support this work were received from the Rochester Center for Alzheimer’s Disease Research (RCADR) and an anonymous donor to identify the key physiological and motion parameters that best track the cognitive decline that occurs in Alzheimer’s. MoBI avatar with human traces.The MoBI system tracks movement and brain activity via electroencephalography (EEG) while subjects are walking and performing tasks. “Walking requires a certain amount of what we would call cognitive load, and the behavioral task also requires a certain amount of cognitive load,” Freedman said. “When you put them together we can uncover the masked deficits.” Researchers are working to identify differences between the brains of younger and older healthy subjects. The goal is to provide researchers with a benchmark against which they can compare motor function and brain activity with those experiencing cognitive decline. “If we can slow the progression of Alzheimer’s down enough so that symptoms start at 90-years-old instead of 80 that would be fantastic. We’re not there yet, but I think that’s the path we’re on.” A path that needed a pilot grant to begin.

Each pilot program supports a specific field of neuroscience. The Schmitt Program in Integrative Neuroscience (SPIN) supports basic science and translational projects that advance understanding of normal and abnormal brain functions. The Harry T. Mangurian Jr. Foundation supports basic, clinical, and translational research projects for Autism Spectrum Disorder. The Rochester Center for Alzheimer’s Disease Research (RCADR) supports basic science and translational projects that advance understanding of Alzheimer’s disease and related dementias. Philanthropic funds within the RCADR support awards aimed at understanding Alzheimer’s – the Feinberg Family Fund and the Sally J. States Pilot Fund in Alzheimer’s Research. The University of Rochester Center for Advanced Brain Imaging and Neurophysiology (UR CABIN) offers support for innovative, investigator-initiated basic and clinical neuroscience research that employ the PRISMA 3T MRI. The Center for Health + Technology (CHET) Clinical Neuroscience Pilot Program offers funding for clinical research projects that leverage novel digital technologies that advance our understanding of areas of unmet need in clinical neuroscience.

The CHET Pilot Program is currently supporting a study that aims to develop a new tool that measures exercise in stroke patients. Ania Busza, M.D., Ph.D. an assistant professor in Neurology who specializes in stroke, was awarded a $49,300 CHET grant for this research in 2019. Flexor - Sensors on arm measure exercise in stroke patient.Using biometric sensors, Busza is designing a tool for the objective measurement of rehabilitative exercise. To date, Busza and her collaborators have developed a machine learning algorithm that accurately identifies when a person is doing one of three basic exercises and counts the number of reps, and are working to expand the number of exercises to 10. “We think it's the first month or two after a stroke that the person has the most potential for plasticity and for improving,” Busza said. “The pilot is allowing us to develop a tool to quantify exercise, movement, and recovery.” Busza has a paper in the pipeline, along with an application for a larger grant that will enable her lab to make improvements to the tool that will allow researchers to better understand the role exercise plays in stroke recovery. “I’m too junior to have a huge pot of funds that I can just play around with and all of the grants I have been applying for seem to want at least some preliminary data to show that we’re able to do what we claim we can do. I needed the pilot to do that.”

Having preliminary data from a study supported by a pilot grant elevated the work of Ania Majewska, Ph.D. She was awarded a $40,000 Schmitt pilot grant in 2015 to study the mechanism that regulates how microglia – part of the brain’s immune system – move in the brain, and whether microglia function to repair or exacerbate damage in the brain following a stroke. Microglia working in the quiescent brain. Green = microglia, purple = microglial receptors at the fine ends of microglial processes.The data collected have since turned into millions of dollars of federal funding, competitive student training grants, and publications – including one in a major research journal. “I really think that in order to understand anything about brain function, whether it’s developmental or computational or disease therapeutics, you need to understand all the different players and how they interact,” Majewska, a professor in the Department of Neuroscience, said. “The biggest thing about having pilot funding is being able to do these experiments and really find out if your ideas are worth pursuing further.” Five years later, data from this pilot continues to branch out. In 2019, a Nature Neuroscience publication was the first to show that microglia shut off while we are awake and likely do their jobs while we sleep. Majewska has also since been awarded multiple NIH grants totaling more than $3 million, and students in her lab have received competitive F30 and F31 grants – totaling nearly $500,000.

A 2020 RCADR Feinberg pilot is supporting novel research by Harris Gelbard, M.D., Ph.D., a professor in the Center for Neurotherapeutics Discovery. Gelbard is investigating changes in the blood and brain after orthopedic surgery that result in post-operative delirium – Brain tissue that is being investigated to determine what type of immune cells are associated with damage and repair (URMC-099) in Gelbard lab with a model of post-operative delirium.research that could have implications for our understanding of Alzheimer’s and dementia. The study aims to identify proteins in immune cells in the body and brain that could be targeted by URMC-099 – an anti-inflammatory and neuroprotective agent developed in Gelbard’s lab. Findings from previous studies have shown this compound can prevent this type of delirium. This new pilot will help gather data necessary for larger studies with the hope of eventually advancing this research to clinical trials. “Pilots are really the lifeblood of investigative science,” Gelbard said. “This is about moving the needle forward, and pilots give you the opportunity to do that. You couldn’t be successful without them.”

Originally published in NEUROSCIENCE Volume 8.

1/28/2021

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