We seek to unravel the mysteries of GPCR signaling in cardiovascular tissues using biochemical and cell biological approaches
The G-protein coupled receptor laboratory in Ashoka University
Know the principal investigator
I am Kasturi Pal, a cell biologist in the laboratory and a foodie, wanderlust struck amateur photographer and oil pastel enthusiast outside of it. I took a strong liking for signaling pathways since my undergraduate years, amazed by the efficiency of cells to amplify signals via second messengers. I still marvel at the flexibility of biological signaling cascades i.e., the meticulous ways in which evolution has tweaked around with the signaling molecules and spatial compartments of cells to ensure that the pathways function as efficiently in vertebrates and invertebrates. I am also fascinated by how these evolutionarily conserved pathways are rewired by stress, mutations and diseases like cancer. Welcome to the GPCR signaling lab in Ashoka University, where we try to understand the cellular information processing machinery.
Research & Discoveries
G-protein coupled receptors (GPCRs) are the largest family of cell surface receptors. Upon stimulation with an appropriate ligand, GPCRs signal to mediate a diverse range of physiological functions ranging from vision, olfaction, gustation, cell migration and even hormonal regulation of metabolism. A significant fraction of FDA approved prescription drugs (~40%) for treating cancer, hypertension or chronic pain targets a type of GPCR.
Some more GPCR trivia- nearly 5% of the human genome codes for GPCRs, which accounts to nearly 800 different GPCRs! Out of these 800 GPCRs, endogenous ligands are unknown for over 140 receptors, making them orphan GPCRs. This leaves a lot of room for research and discovery!!
In our lab, we seek to unshroud the mysteries surrounding these dynamic molecules. The multidisciplinary nature of our research laboratory has been the major strength of our research. Keep reading to find out what we are currently working on.
Determining the temporal and spatial origin of platelet GPCRs
Platelets are anucleate cells originating from precursor cells called megakaryocytes. Platelets prevent blood loss following injuries by initiating complex singling pathways to bring about blood coagulation to form a clot which seals off injured blood vessels. GPCRs are serpentine protein receptors on platelet membranes which play pivotal roles in clot formation. However, it is unknown how and when GPCRs are expressed in anucleate platelets. We are employing proteomics, next generation sequencing and imaging approaches to determine the origin of GPCRs during the megakaryocyte to platelet differentiation pathway
How do adhesion GPCRs transduce force?
According to the GRAFS system of GPCR classification, the largest family of membrane proteins are grouped into 5 categories: (1) Glutamate, (2) Rhodopsin, (3) Adhesion, (4) Frizzled and (5) Secretin types. Of these, the adheison GPCR are known to possess very long extracellular N-terminus domains with cadherin, leucine rich repeats and EGF-like domains which are known to facilitate protein-protein interaction necessary for cell-cell or cell-matrix adhesion. They have been implicated in embryonic heart and brain development. It has also been speculated that some adhesion GPCRs are mechanosensory. However, due to the complex nature of the adhesion GPCR genes and the large size of the protein, they remain the least studied of the all the GPCR categories. It is currently unclear how adhesion GPCR respond to force. We are collaborating with Dr. Haldar's laboratory in Ashoka University to answer this long standing question by employing single molecule experiments, imaging, cell based assays and flow cytometry
Role of GPCR dimerization in regulating sonic Hedgehog signaling
The primary cilium is a specialised sub-cellular compartment originating from the apical surface of cells using the basal body as a template. It is indispensable for the functioning of the Sonic Hedgehog pathway, since all the key proteins of this evolutionarily conserved signaling cascade traverse though this compartment. The major positive and negative regulators of the pathway are the 2 GPCRs Smoothened and Gpr161 respectively. It has recently been shown that Smoothened entry into the primary cilia is mandatory for the ciliary exit of the negative regulator Gpr161. However, the molecular mechanism underlying the reciprocal relationship between Smoothened and Gpr161 remain elusive. In collaboration with Dr. Durba Sengupta in NCL, Pune we are employing in-silico approaches to map putative interaction sites between the two receptors.
We are grateful to DBT India and intramural funding from Ashoka University
Thank you for your interest in our research. Get in touch with us for any questions or comments regarding our work, reagents and publications. We are located on the 2nd floor of Ashoka Science Block
Plot # 2, Rajiv Gandhi Education City
Sonipat, Haryana 131029