Dr Pijush Chakraborty

Profile

Bachelor of Science (B.Sc.) with Honours in Chemistry from University of Calcutta, India (2012-2015)

Master of Science (M.Sc.) in Chemistry from Indian Institute of Technology (IIT) Bhubaneswar (2015- 2017)

Ph.D. in Biology from German Center for Neurodegenerative Diseases (DZNE) Göttingen, Germany (Degree awarded by The Georg-August-Universität Göttingen, Göttingen, Germany) (Dec, 2021)

Postdoctoral Researcher at German Center for Neurodegenerative Diseases (DZNE) Göttingen, Germany (Jan 2022 – Sept 2022)

Postdoctoral Researcher at Max Planck Institute for Multidisciplinary Sciences (MPINAT) Göttingen, Germany (Oct 2022 – Dec 2023)

Research interests

Ph.D. research

During my Ph.D., my research focused on the Alzheimer's disease-related protein tau. We developed an in vitro protocol to aggregate the full-length tau protein without co-factors, marking the first demonstration that tau protein can form amyloid fibrils in vitro in the absence of any negatively charged molecules. Using NMR spectroscopy, we characterized these co-factor-free tau fibrils and discovered that they have the same core structure as brain-derived fibrils from patients with Corticobasal Degeneration (CBD). Furthermore, employing this co-factor-free aggregation assay, we investigated the effect of acetylation on the aggregation of 3R and 4R isoforms of tau. We found that acetylation strongly attenuates 4R tau aggregation but promotes 3R tau aggregation, suggesting that acetylation is a crucial regulator driving the selective aggregation of 3R tau and the development of 3R tauopathies such as Pick’s disease.

First Post-Doctoral research

In my first post-doctoral position, we performed a detailed characterization of the interaction between tau protein and the Hsp90 co-chaperone FKBP12 using NMR spectroscopy. We revealed that FKBP12 enhances neuronal resilience by chaperoning a specific structure in the monomeric tau protein. In another project, we demonstrated that phosphorylation of tau by GSK3β kinase, unlike several other kinases, promotes tau aggregation through enhanced phase separation. Cryo-EM analysis revealed that the amyloid fibrils formed by GSK3β-phosphorylated tau adopt a fold comparable to paired helical filaments isolated from the brains of Alzheimer's disease patients. Additionally, we uncovered an Hsp90-independent mechanism in which a molecular complex of two Hsp90 co-chaperones, p23, and FKBP51, chaperones tau aggregation. Using NMR spectroscopy, SAXS, molecular docking, and site-directed mutagenesis, we elucidated the structure of the p23-FKBP51 complex.

Second Post-Doctoral research

Currently, in my second post-doctoral position, we are researching Type-2 diabetes-related amyloid fibril-forming protein IAPP. We have identified several small molecules as potential inhibitors of IAPP amyloid formation and are structurally characterizing the interactions between IAPP and these small molecules using NMR spectroscopy. In a separate project, we are investigating Parkinson’s disease-related amyloid fibril-forming protein α-synuclein. We are characterizing the effects of different aggregation-inhibiting and -promoting mutants on the transient structures formed by α-synuclein using NMR spectroscopy.

Student education