Profile
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 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.
Current Focus Areas
Selected Publications
Ambadipudi, S., Jithender G.R., Jacek, B., Mandelkow, E., and Zweckstetter, M (2019). Residue-specific identification of liquid phase separation hot spots of the Alzheimer’s disease-related protein Tau. Chemical Science, 10: 6503-07
Ambadipudi, S., Jacek, B., Riedel, D., Mandelkow, E., and Zweckstetter, M (2017). Liquid-liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau. Nature Communications 8(1): 275
Gaur, R.†, Ambadipudi, S.†, Chary, K.V.R., and Mishra. L (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)
Tiwari, V., Ambadipudi, S., and Patel, A.B (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
Chakraborty, S., Ambadipudi, S., and Hosur, R.V (2012). Selective lighting up of segments around Gly, Ala and Ser/Thr in proteins. Magnetic Resonance in Chemistry, 50(9):587-91