Sindhuja Sridharan, PhD

Profile

Sindhuja Sridharan is a systems biochemist who is interested in understanding how alterations in molecular interaction networks of proteins are wired in physiology and disease. She completed her doctoral studies in the lab of Prof. Manjunatha Kini at the National University of Singapore (NUS) where she characterized the action mechanism of bioactive peptides and further engineered them for personalized treatment of heart failure.  To gain a systems perspective of biology, she moved to Germany to join the lab of Dr Mikhail Savitski, at European Molecular Biology Laboratory (EMBL) and Dr Marcus Bantscheff, at GlaskoSmithKlein (GSK). Here, she used and developed proteome-wide technologies that allows the in-situ measurement of protein interactions with other proteins, metabolites and nucleic acids to understand their role in context-dependent cellular functions.

Research

Research Interests:

We are interested in understanding how cellular metabolism and protein condensation are interlinked to the pathogenesis of brain tumour. Many genetic alterations discovered in brain tumours are known to rewire metabolic pathways and/or alter propensity of proteins to form biomolecular condensates. However, how metabolic alterations manifest as biochemical changes within the cellular environment remains understudied. Brain tumour is a dynamic microenvironment with several cell types (neuron, astrocyte, glioma cell and microglia) interacting with each other. The metabolic output of one cell type can vastly influence and reprogram systems within the cellular community. Our group aims to address the following open questions to provide insights into the pathogenesis of brain tumour using quantitative proteomics based systems biology approaches:

(a)    how do activity-altering genetic mutations of key metabolic enzymes remodel cellular processes?
(b)    how do cellular compartment specific variations in metabolite pools affect gene expression?
(c)    how does the metabolic output of one cell type influence the other cell types within the tumour microenvironment?

Publications

Key Publications

S Sridharan, A Hernandez-Armendariz, N Kurzawa, C.M Potel, D Memon, P Beltrao, M Bantscheff, W Huber, S Cuylen-Haering, M.M Savitski. 2022. Systematic discovery of biomolecular condensate specific protein phosphorylation. Nature Chemical Biology. DOI: https://doi.org/10.1038/s41589-022-01062-y

X Zhang*, S Sridharan*, I Zagoriy, C.E Oegama, C Ching, T Pflaesterer, H.K.H Fung, I Pose, C.W Mueller, A.A Hyman, M.M Savitski, J Mahamid. 2022. Molecular mechanisms of stress-induced reactivation in mumps virus condensates.
DOI: https://doi.org/10.1101/2021.07.10.451879 

T Maatta, M Rettel, S Sridharan, D Helm, N Kurzawa, F Stein, M Savitski. 2020. Aggregation and disaggregation features of the human proteome. Molecular Systems Biology. 16:e9500. DOI: doi.org/10.15252/msb.20209500

S Sridharan*, N Kurzawa*, T Werner, D Helm, I Guenthner, W Huber, M Bantscheff, M Savitski. 2019. Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles of ATP. Nature Communications. 10(1):1155.
DOI: doi.org/10.1038/s41467-019-09107-y

S Sridharan, R.M Kini. 2018. Decoding the molecular switches of natriuretic peptides which differentiate its vascular and renal functions. Biochemical Journal.  75(2) 300-413. DOI: doi.org/10.1042/BCJ20170690

* equal contribution
Full list of publications: Google Scholar