Team

Principal Investigator

Dr Indrajit Sahu, Phd

My broad research interest is to understand the mechanism of protein degradation by Ubiquitin-Proteasome-System (UPS) in human 3Ds – Disease, Disorders & Development. The UPS is the major protein degradation machinery in all eukaryotes responsible for the timely degradation of the damaged, unused and retired proteins Thereby it regulates almost all cellular signaling pathways during normal and diseased settings. Despite the extensive involvement of Proteasomes in human pathologies and being a potential hotspot for target therapy, we are lacking the deeper understanding on the Proteasome functionality under disease conditions.

Phd Students

Suraj Kumar

CSIR-JRF

Having a hypoxic microenvironment is a common and salient feature of most solid tumours which severely affect the cancer prognosis, diagnosis and the modern therapeutic modalities. Understanding the synergistic relationship between hypoxia and cancer has become an emergent demand. Since proteasome activity and integrity is highly dynamic in hypoxia and can deregulate the cancer cell physiology, we would like to investigate how hypoxic cancer cells manipulate the proteasome function for survival. If we could understand these proteasome impairments, a better therapeutic strategy can be developed to tackle solid tumours

Madhuparna Karmakar

UGC-JRF

Activating Ubiquitin-mediated Proteasomal System for the treatment of Alzheimer's disease

Ravish Javed

UGC-JRF

Understanding the alteration in structural and functional dynamics of host macromolecular complexes upon virus infection is crucial in understanding disease mechanism. My doctoral research is centered on investigating how one of the most vital proteases of SARS-CoV2 influence the human Ubiquitin Proteasome System (UPS) and alter host protein homeostasis.

Adarsh Mala

DBT- JRF

The 26S proteasome is the primary ubiquitin-dependent degradation machinery in eukaryotic cells. In contrast, the 20S proteasome, which constitutes ~50% of cellular proteasomes, acts as an emergency system under hypoxic stress and can degrade both unstructured and globular proteins despite lacking defined substrate-binding sites and unfoldase activity.

My project aims to understand how the 20S proteasome recognizes and unfolds its substrates for proteolysis.

Diya Aich

DBT- JRF

My doctoral research focuses on investigating the proteasomal plasticity and ubiquitin landscape remodeling during stem cell differentiation.

Stem cells are maintained through a tightly regulated network of transcription factors, signaling pathways, epigenetic mechanisms, metabolism, and proteostasis. My project focuses on the role of Ubiquitin-Proteasome system in this context, focusing on how proteasomal alterations and differential ubiquitination maintains pluripotency and regulates cell fate decisions.

Project JRFs

Dhanisha Mohapatra, ICMR-JRF

Drug repurposing is an upcoming frontier in medical research as it reduces the cost & time required when compared to developing novel molecular entities. Since the safety profiles & pharmacokinetics of these drugs are already known, it can be utilized for treating other disorders with unmet needs. My project studies about such FDA approved drugs that can be repurposed for treating Alzheimers' disease using Drosophila melanogaster as the animal model. My research investigates whether these drugs can enhance the cell's natural protein clearance system, the ubiquitin-proteasome pathway, to remove harmful proteins that accumulate in Alzheimers' disease.

Project Trainees

Rutuja Patil

My research explores the interaction between SARS-CoV-2 NSP3 and Human Ubiquitin Proteasome System to understand its impact on cellular protein homeostasis. Insights from this work may help elucidate the role of this interaction in viral immune evasion

Archita Mangale

My project focuses on understanding the role of a 19S lid protein in maintaining 26S proteasome integrity in mammalian cells. Although this protein has been shown to promote 19S lid assembly and stable 26S proteasome formation in primitive models, its role in mammalian cells remains unexplored. By altering its levels, I aim to determine how it influences proteasome integrity and, consequently, its activity.

Past Lab Members

Lipika Sahu

My study focuses on the interaction between one of the vital Deubiquitinating Enzymes (DUBs) of USP family via the UBL domain and the 26S Proteasome complex. The work highlights the structural aspects underlying their binding interface. This will provide insight into the molecular basis of DUB–proteasome interaction.

Ananya Jain

Understanding how ubiquitin chain topology is dynamically regulated is essential to decoding cellular proteostasis. My project investigates how deubiquitinases (DUBs) sculpt ubiquitin architecture under basal conditions. I aim to identify constitutively edited substrates and define how disruption of DUB function reshapes the cellular ubiquitin landscape.