Research Focus

The nuclear pore complexes (NPCs) embedded in nuclear membrane bilayer solely mediate transport of all kind of macromolecules between nucleus and cytoplasm, and regulate nearly most cellular processes such as gene expression, mitosis, cell differentiation etc. Additionally, alternations in NPC and its associated proteins have been linked to several human diseases, such as cancer, genetic disorders and viral diseases. The architecture of the NPC is evolutionarily conserved and is a highly modular structure.

The nuclear pore complexes (NPCs) embedded in nuclear membrane bilayer solely mediate transport of all kind of macromolecules between nucleus and cytoplasm, and regulate nearly most cellular processes such as gene expression, mitosis, cell differentiation etc. Additionally, alternations in NPC and its associated proteins have been linked to several human diseases, such as cancer, genetic disorders and viral diseases. The architecture of the NPC is evolutionarily conserved and is a highly modular structure. Each NPC is comprised of ~30 different proteins called nucleoporins (Nups) that are arranged in multiple copies to yield a size of 65 MDa (yeast) or 125 MDa (vertebrate). In order to understand the molecular mechanisms of NPC assembly formed by these ~30 Nups and its versatile functions, the high-resolution structures are highly desired but complexity and the size of the NPCs pose tremendous challenges. A rational strategy therefore would be to disintegrate the components of NPC based on their structural and functional specificity and employ integrative approaches to learn about the roles of Nups in NPC assembly and cellular physiology. Our laboratory routinely utilizes various structural biology tools such as X-ray crystallography, electron microscopy and spectroscopy methods and we work in collaboration with cell biologists to understand the versatile functions of NPCs, such as how Nups participate in nucleocytoplasmic transport, gene regulation and cell differentiation.

Ongoing Research Projects:

1. Biochemical reconstitution and structural studies of human nucleoporin sub-complexes of the NPC

We are pursuing biochemical reconstitution and atomic resolution 3D structure determination of human Nup93 subcomplex, also known as inner ring complex and Nup62 sub-complex (known as central transport channel, CTC). We deciphered precise interaction regions of mammalian Nup93 that can be biochemically assembled with ordered region of Nup62•Nup54•Nup58 complex and showed EM structure using negatively stained method. We also demonstrated how the dynamic nature of the CTC complex is conserved across the species yet maintaining the species specific features.
See Biochemistry 2017, Protein Science 2019, Protein Science 2020

We also successfully reconstituted mammalian Nup88•Nup62•Nup214 complex and revealed the scaffold/hub role of Nup62 coiled-coil mediated heterotrimer formation with other Nups and such heterotrimers can be recognized by Nup93 based on 3D shape (biorxiv 2022)

We use cryo-EM Single particle analysis based methodologies to determine atomic resolution structure of human Nups, such as Nup155 (Biorxiv 2021) that revealed a biochemical consequences of a genetic mutation (R391H) to cause atria fibrilliation.

2. Crosstalk of NPC with viral proteins

We are pursuing the physical interactions of human Nups with viral factors to elucidate the underlying role of the NPC in viral infections such as HIV-1. (Cells 2019)

3. Developing innovative methods in protein-protein interactions

Using the combination of biochemical methods and machine learning computational tools we are actively pursuing development of new methods to decipher interacting network of multiprotein complexes. Our efforts in this area led us to come up with a tool (CoRNeA) that can predict interacting regions between two partners solely based on their primary sequences. Such method is extremely beneficial in biochemical reconstitution of the multimeric proteins (Biomolecules 2020).

OUR RESEARCH HIGHLIGHTS

                   COVER PAGE OF BIOCHEMISTRY, 2017                                Highlights  of Protein Science, 2019 showing supertree of the NPC

Highlights of Protein Science, 2020 issue showing architecture of mammalian CTC•Nup93 complex

Publications

2012 Onwards

Before 2012:

For latest publications :

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Awards/Honours/Memberships

• DST/SERB Ramanujan fellowship 2012
• DST young scientist award 2003
• CSIR young scientist award 2002
• CSIR NET fellowship 1998-2003

Funding/Collaborations

Our laboratory research is funded by Department of Biotechnology and Department of Science and Technology India.
Radha Chauhan is Ramanujan Fellow

Lab Members

Virashree Jamdar, Technician C, virashree29@nccs.res.in

PhD Students

Postdoctoral Associate

Alumni

B.S./M.Tech/M.Sc training students and project students trained in the lab:

Opportunities:

Postdoctoral position: Highly motivated scientists interested in protein structure and function with strong background in cell biology, biochemistry and/or molecular biology or bioinformatics methods are always encouraged to apply. Inquire by email to Radha Chauhan

Ph.D positions: Prospective graduate students interested in our research (structural, computational and cellular biology) should apply through our regular Ph.D. program at NCCS and contact Radha Chauhan for possibilities of research projects.

2-12 months training: Students interested in MS/M.Sc project training projects, please email us at academics@nccs.res.in