Exploring the ‘Dark Matter’ of the Cell

Tom Maresca recently received a four-year, $1.3 million grant renewal from the National Institute of General Medical Sciences to use specialized tools to learn more about the less-studied inner universe of the cell.

There is a little-understood realm inside cells that cell biologist Tom Maresca likes to think of as the cell’s dark matter, something like the largely unknown stuff that is so abundant in space.

He explains that a foundational aspect of how scientists think about biology is called the structure-function paradigm, referring to how many proteins adopt specific and highly reproducible folded shapes that allow them to carry out their functions. For these, shape and function are inextricably linked. “These would be analogous to regular matter and they can be studied with conventional biochemical methods and techniques like X-ray crystallography and cryo-electron microscopy,” Maresca says.

“But there are also many proteins that are predicted to have no specific structure, and they’re not as easy to study as well-folded proteins. They’re called intrinsically disordered proteins, which means they are unstructured,” he adds.

Sometimes referred to as the Dark Proteome, these shapeless proteins “appear to be very abundant, we just don’t know much about them. There’s been tremendous progress in understanding structure-function; now we hope to make progress in this other important area of how unstructured proteins function.”

For the new grant, Maresca and colleagues will collaborate with biophysicist Nathan Derr at Smith College.

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