NERD grant of DKK 13 million to Himanshu Khandelia from Department of Physics, Chemistry and Pharmacy

In biophysics, Himanshu Khandelia’s research combines computations, physics, chemistry and biology to study the molecular machinery that keeps cells alive.

With a NERD grant of DKK 13 million from the Novo Nordisk Foundation, he can now focus on an ambitious plan to create the first comprehensive map of how mitochondria move vital molecules across their membranes.

According to him, “This could strengthen future research into very different diseases, ranging from metabolic diseases and neurological disorders to cancer”. Examples of other diseases are cancer, hyperinsulinism and citrin deficiency.

Unknown proteins

Mitochondria are often described as the power plants of our cells. To generate energy and keep cells functioning, they constantly exchange nutrients, signaling molecules and other compounds with the rest of the cell.

This traffic is controlled by a group of proteins known as SLC25 transporters.

“Although they are essential for life, we still know remarkably little about how most of them work. We want to change that, and my aim is to create an atlas of the entire SLC25 family”, writes Khandelia, calling such an atlas “transportome”.

Severe consequences

The human body contains 53 known SLC25 transporters. They act as microscopic gatekeepers that control the movement of substances into and out of mitochondria.

"When these transporters do not function properly, the consequences can be severe. Mutations in these proteins have been linked to a growing range of metabolic and neurological diseases," writes Himanshu Khandelia.

Researchers currently understand the molecular mechanisms of only two of the 53 transporters in detail.

Using super computers

For the remaining proteins, key questions remain unanswered: Which molecules do they transport? How do they recognize their cargo? And how and why do disease-causing mutations disrupt their function?

To answer these questions and create the atlas, Khandelia plans to large-scale molecular simulations performed on some of Europe's most powerful supercomputers.

The atlas will be a publicly available resource that researchers worldwide can use to study mitochondrial biology and disease.

Project title: MitoPort: Mechanisms of Mitochondrial Transport in Metabolic Disease.