Margaret Stratton ponders a conundrum as she and her students study neuronal proteins in her lab: how does memory survive the molecules that encode it?
“The cells in the brain persist for a long time, so we can understand at the cellular level how memories can last for decades,” says Stratton, associate professor of biochemistry and molecular biology. “But the components in these cells are constantly being recycled — proteins in particular are being broken down and remade on the order of seconds to hours, maybe weeks, but certainly not years.”
To further her research on this big question, Stratton received a five-year, $1.8 million grant from the National Institute of General Medical Sciences as part of the Maximizing Investigators’ Research Award (MIRA) program. MIRA grants are designed to increase the scientific productivity of talented and promising scientists and increase the chances of major breakthroughs.
Stratton studies ca2+/Calmodulin-dependent protein kinase II (CaMKII), a calcium-sensitive protein encoded by four mammalian genes.
“We know from mouse experiments and also from mutations found in humans that this protein is really crucial for learning and memory,” explains Stratton.
The ultimate goal is to understand how long-term memory works at the molecular level by investigating how CaMKII can act as a hub in neurons to maintain molecular signals over a long period of time.
“Once we get that under control, hopefully it will provide us with opportunities to intervene therapeutically when something goes wrong, either because of a mutation in that specific protein or because of mutations in other proteins that affect long-term memory,” says Stratton.
The research has applications beyond understanding the molecular basis of memory, as CaMKII is also found in other calcium-coupled cells in the body, including cardiomyocytes in the heart and ova in the ovaries.
Stratton and her team will use sequencing, biochemistry, structural biology, and cellular assays to study the role of CaMKII in different cells and how this one enzyme enables such multifunctionality.
“The cool thing is that the versions of the protein found in these different cells are actually quite similar,” she says. “So what we learn in one system also informs us in the other systems.”
Once there is a better understanding of the molecular mechanisms, researchers can aim to develop treatment approaches for a range of diseases.
The research promises “far-reaching implications for therapeutic intervention in neurological diseases, cardiac dysfunction and infertility,” according to the funding summary.
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