Ion Channels and Cell Signalling Pathways

Our Research

The lab is situated in the department of biological sciences and bio-engineering (BSBE) at IIT Kanpur. Here at BSBE, our research is primarily focused on developing a comprehensive understanding of membrane-spanning calcium ion channels, including TRP channels. These channels facilitate calcium signaling that controls a myriad of physiological functions, including sensory modalities of the body such as temperature and pain sensation, neuronal excitability, bone formation, cell proliferation, and apoptosis. Therefore, the tight regulation of intra- and extracellular Ca2+ levels is crucial for living organisms. Indeed, alteration in calcium homeostasis leads to a number of devastating diseases, including cancers.

We use x-ray crystallography and cryo-electron microscopy to determine the structure of ion channels and then validate the structural findings with functional approaches, including electrophysiology, single ion channels recordings, and mutagenic and chimeric approaches.

Our collaborative study with kirill's lab at scripps is published in 'Science'

We used cryo-electron microscopy to determine the atomic resolution structure of an orphan receptor called GPR158, which is expressed in the brain. The malfunction of this receptor either by naturally occurring mutations or overexpression is implicated in depression and anxiety. We resolved the molecular architecture of GPR158 alone and complex with its binding partner, RGS signaling protein. Surprisingly, the structure revealed the existence and physiological importance of a unique domain- the Cache domain, which is prevalent in bacterial chemoreceptors for sensing diverse small compounds, including amino acids.

Auxin signaling in human

The auxin signaling is well-known for its involvement in plant, its function in non-plant species remains poorly understood due to lack of evidence for auxin binding and transport proteins. Recently, we have discovered an auxin transporter, GPR155, also known as LYCHOS (Lysosomal Cholesterol Signaling), which is a unique lysosomal membrane transceptor that combines a G-protein coupled receptor (GPCR) domain with transporter domains. More specifically, we have demonstrated that GPR155 is crucial for cholesterol signaling and auxin transport within lysosomes, functioning as a cholesterol sensor that activates mTORC1 in a cholesterol-dependent manner. We used cryo-electron microscopy to determine the atomic resolution structure of an orphan receptor called GPR155, which is expressed in the brain. Structure of GPR155 closely resembles to the PIN-formed auxin transporter from plants, raising the possibility of auxin sensing in humans. We believe that exploring the non-canonical auxin-cholesterol signaling axis in neurons could unlock new therapeutic avenues for treating neurological disorders.

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