Aug 22, 2024 03:46 PM IST
Aravind Penmatsa of the Indian Institute of Science, Bengaluru, describes his work with membrane proteins in neurons.
Both winners in the Biological Sciences category of this year’s Yuva Vigyan Shanti Swarup Bhatnagar awards study membrane proteins, molecules in the cell membrane that transport materials and exchange signals. Aravind Penmatsa of the Indian Institute of Science, Bengaluru, describes his work with membrane proteins in neurons.
What I do
We study a type of membrane protein in neurons, the cells involved in fundamental brain physiology and behaviour. Membrane proteins are macromolecules (molecules made of a large number of atoms) embedded in the membrane, the boundary around all living cells. While the membrane keeps the cellular contents from mixing with the extracellular environment, cells also have to react to extracellular signals, absorb nutrients and release toxic substances that accumulate within them. These roles are performed by different types of membrane proteins, which are involved in transport of various kinds of materials, and can also act as receptors of external signals and initiate signalling within the cell.
In neurons, the membrane proteins that are particularly important are transporters, ion channels and receptors. We study transporters of neurotransmitters. Neurotransmitters are “messengers” that carry signals from one neuron to another, and the membrane proteins that transport them help control the level of communication between neurons. It is important to study neurotransmitter transporters because they can be targeted by different drugs to alter neural activity in some disorders, such as depression, pain, addiction and anxiety.
How I do it
Many available antidepressants, anxiety and pain-relief medications are already known to target neurotransmitter transporters. However, it is not always clear how they interact with the target membrane proteins.
Our work gives a very detailed insight into the architectural organisation of these molecules. This allows us to map the location and mechanisms of drugs that block transport or channel activity. This information is extremely important for developing more specific drugs, and develop molecules that can track the location of the transporters in the cellular membranes.
Our work has focused on some pain-relief medication that works by increasing the levels of a neurotransmitter called noradrenaline between neuronal junctions. We have identified the pockets in the transporters where these drugs bind, and deciphered how certain blockers can specifically target the transport of noradrenaline. We have also looked at how antiepileptic medications target another neurotransmitter, GABA, and how these blockers specifically bind to GABA transporters.
