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Architecture of phosphoinositide signalling systems

Our long-term scientific interest is to understand cellular communication strategies mediated by lipid molecules generated by the metabolism of phosphatidylinositol. These lipid signals, called phosphoinositides (PIs), provide molecular control for key sub-cellular processes such as membrane remodeling, cytoskeletal function, transcription and translation. Through these processes, PIs orchestrate basic cellular behaviors such as cell division, shape changes, polarized movement and cell death and thus play a key role in several physiological processes including early embryogenesis, lymphocyte development and function as well as neuronal activity. The spatial and temporal levels of PIs are controlled by a set of evolutionarily conserved kinases and phosphatases and mutations in these genes are known to result in several human diseases. The overall goal of our work is to understand how the architecture this signaling cascade is designed to optimally deliver physiological outputs. We have a particular interest in understanding the control of cellular neurobiology and human brain diseases by PI signaling.

We also study the function of phosphoinositides in neuronal cell biology and brain disorders using human genetics and iPSC derived neural cell models in cell culture. The goal of this work is to uncover the function of altered phosphoinositide signaling in controlling neuronal cell biology and changes in these that may underlie human brain disorders.

Our work on brain disorders is done in collaboration with clinicians at St. John’s Medical College, Bangalore and the National Centre for Mental Health and Neurosciences, Bangalore. Our lab participates in the Rohini Nilekani Centre for Brain and Mind.

Selected Recent Publications

1.     Saha S, H Krishnan H, Raghu P*. IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium. Life Sci Alliance 2023 Dec 6;7(2):e202302425. doi: 10.26508/lsa.202302425. Print 2024 Feb.

2.     Ghosh A, Venugopal A, Shinde D, Sharma S, Krishnan M, Mathre S, Krishnan H, Saha S, Raghu P*. PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase. Life Sci Alliance. 2023 Jun 14;6(9):e202301920. doi: 10.26508/lsa.202301920. PMID: 37316298

3.     Akhtar BM, Bhatia P, Acharya S, Sharma S, Sharma Y, Aswathy BS, Ganapathy K, Vasudevan A & Raghu P*. A human stem cell resource to decipher the biochemical and cellular basis of neurodevelopmental defects in Lowe Syndrome. Biology Open 2022 15;11(1):bio059066. doi:10.1242/bio.059066 

4.     Kumari A, Ghosh A, Kolay S and Raghu P*. Septins tune lipid kinase activity and PI(4,5)P 2 turnover during G-protein-coupled PLC signalling in vivo. Life Sci Alliance. 2022 Mar 11;5(6):e202101293.  doi: 10.26508/lsa.202101293.

5.    Trivedi D , Vinitha CM , Bisht K , Janardan V, Pandit A, Basak B, Shwetha H, Ramesh R , & Raghu P*.. A genome engineering resource to uncover principles of cellular organization and tissue architecture by lipid signaling. eLife. 2020 Dec 15;9:e55793.

6.    Nath VR, Basak B, Mishra S, Trivedi D and Raghu P*. Extended synaptotagmin regulates membrane contact site structure and lipid transfer function in vivo. 2020. EMBO Reports. 27 July. e50264.

7.   Raghu P*, Basak B & Krishnan H. Emerging perspectives on multidomain phosphatidylinositol transfer proteins. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids; Lipid Transfer Proteins (2021) 2021 Sep;1866(9):158984. doi: 10.1016/j.bbalip.2021.158984. Epub 2021 Jun 9.PMID: 34098114

8.    Raghu P*. Emerging cell-biological functions of phosphatidylinositol 5 phosphate 4 kinase. Curr Opin Cell Biol. 2021 Mar 4;71:15-20. doi: 10.1016/