$2.8M NIH Grant Targets Proteins Involved in Brain Disorders

$2.8M NIH Grant Targets Proteins Involved in Brain Disorders

The National Institute of Neurological Disorders and Stroke, of the National Institute of Health (NIH), has awarded a large grant to researchers who are seeking to understand the molecular structure of toxic proteins that drive brain disorders.

Irregular clumps of certain proteins are thought to be the root cause of several neurological disorders: alpha-synuclein and amyloid-beta proteins are linked with Parkinson’s disease and Lewy body dementia (which often occur simultaneously), and amyloid-beta and tao are involved in Alzheimer’s disease.

The new grant awards $2.8 million over five years to study the structure of these proteins. The project is being led by researchers at Mayo Clinic’s Florida Campus and at Columbia University in New York.

The researchers plan to use new imaging technologies, namely single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), to investigate these proteins in more detail than ever before.

Cryo-EM — a technology that shared the 2017 Nobel Prize in Chemistry — uses beams of electrons to investigate the structure of proteins with atomic-level resolution. Researchers plan to use it to view proteins in samples of brain tissue from people with neurological disorders like Parkinson’s.

Cryo-ET allows for the visualization of proteins within living neurons, which  researchers hope will provide important information about how these protein clumps end up killing brain cells.

“To truly understand the link between proteins and disease, we must discover how they interact with each other and with the surrounding brain tissue,” one of the researchers who will lead the project, Anthony Fitzpatrick, PhD, a professor at Columbia, said in a press release. “Cryo-EM’s power lies in its ability to reconstruct any protein at the level of individual atoms. This, combined with cryo-ET, which helps us understand how each protein behaves inside individual brain cells will, ultimately, enable us to learn how this behavior causes cells to die,” he said.

“[W]e hope to discover whether different proteins work in concert to spur disease progression,” Fitzpatrick added. “The combined use of cryo-EM and cryo-ET marks a tremendous leap forward from traditional, in vitro methods, which study the proteins’ behavior in a petri dish and thus do not replicate their natural environment.”

“One of the most imperative quests of our time is the understanding of brain function and the mechanisms of neurodegeneration,” said Rui Costa, DVM, PhD, the director of Columbia’s Zuckerman Institute. “This endeavor will allow us to have unprecedented insight into the 3D molecular structure of the aggregates that form in many neurodegenerative disorders, which ultimately can be critical for early diagnosis, prevention and treatment of these disorders.”

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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