Research

We are an interdisciplinary research group, interested in understanding how the biomolecules are assembled in living cells and how these assemblies are regulated in function and disease. Biomolecules including proteins, nuclei acids and metabolites are dissolved in cellular fluid and condense into ‘oil-like’ droplets via liquid-liquid phase separation (LLPS). These biomolecular condensates spontaneously assemble and disassemble in response to various cell stimuli. The entire process of LLPS is tightly regulated in normal cells. Dysregulation of biomolecular condensation manifests as diseases like cancer and neurodegeneration. This area of disease biology is new and offers avenues for studying disease mechanisms with a different perspective and has potential for novel therapeutics. Our research focus is on elucidating the mechanisms of biomolecular LLPS in disease, at atomic-level precision. To this end, we combine structural biology with biophysics and cell-based metabolic screening. We obtain the structural architecture and mechanisms of biomolecular condensation by a combination of solution NMR spectroscopy and optical spectroscopy and microscopy methods. We evaluate the relevance of in vitro observations in cellular context from biochemical analyses and NMR-based metabolic studies. We are also interested in designing simplified cell models of diseases and establish artificial-cell platforms for rapid screening of drugs for efficacy and bio-feasibility.

Publications

• Susmitha Ambadipudi, Jithender G Reddy, Jacek Biernat, Eckhard Mandelkow and Markus Zweckstetter (2019). Residue-specific identification of liquid phase separation hot spots of the Alzheimer’s disease-related protein Tau. Chemical Science, 10: 6503-07
• Susmitha Ambadipudi, Jacek Biernat, Dietmar Riedel, Eckhard Mandelkow and Markus Zweckstetter (2017). Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau. Nature Communications 8(1): 275
• Ruchi Gaur^†, Susmitha Ambadipudi^†, KVR Chary and Lallan Mishra (2014). Water soluble Calcium-Sodium based coordination polymer: Selective release of Calcium at specific binding sites of protein. RSC Advances, 4(46):24038-41 (^† Equal contribution)
• Vivek Tiwari, Susmitha Ambadipudi and Anant B Patel (2013). Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain. Journal of Cerebral Blood Flow and Metabolism, 33(10):1523-31
• Swagata Chakraborty, Susmitha AL and Ramakrishna V Hosur (2012). Selective lighting up of segments around Gly, Ala and Ser/Thr in proteins. Magnetic Resonance in Chemistry, 50(9):587-91
• Kousik Chandra, Susmitha AL, Yogendra Sharma and KVR Chary (2010). Structural basis for Ca²⁺ displacement by a paramagnetic ion Ce³⁺ in non-myristoylated neuronal calcium sensor-1. Indian Journal of Chemistry, 50A:539-47
• Susmitha Ambadipudi and Markus Zweckstetter (2016). Targeting intrinsically disordered proteins in rational drug discovery. Expert Opinion in Drug Discovery, 11(1):65-77
• Anant B Patel, Vivek Tiwari, A Susmitha and K Varadarajan (2010).  NMR investigations of excitatory and inhibitory neurotransmission in mouse brain. Proceedings of International society for Magnetic Resonance in Medicine, p-2387 (Sweden, May 1-7, 2010)

Funding and Collaborations

DBT-Ramalingaswami Re-entry fellowship

DST-SERB Core Research Grant

Collaboration: Dr. G. Jithender Reddy, CSIR-Indian Institute of Chemical Technology

Research Group

Bhargavi Ajay Vanjara (UGC-JRF, Ph.D- 2023 – present)

Samarpit Kadam (Masters dissertation, 2023- present)

Tarzan Mohanta (UGC-SRF, Ph.D- 2020 – present, joint student from CSIR-IICT, Hyderabad)

Kasam Vishali (ICMR-SRF, Ph.D- 2021 – present, joint student from CSIR-IICT, Hyderabad)

Sriram Uday R.V (DST–PA II, Ph.D– 2022 – present, joint student from CSIR-IICT, Hyderabad)