The overarching research goal of Dr. Soumya De's laboratory is to decipher the structural and dynamic principles that govern protein functions and their regulation. This is achieved using solution NMR spectroscopy and other biophysical methods that characterize the structure and dynamics of proteins.
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Regulation of HOX transcription Factors: Transcription factors play central role in many biological processes that range from cell cycle progression to cell differentiation and organism development. Hence, it is not surprising that the functions of these proteins are under tight regulation and their disruption lead to several diseases raging from developmental disorders to cancer. Regulatory mechanisms of these proteins include post-translational modifications, protein partnerships and DNA-binding autoinhibition.

In particular, we are investigating the molecular basis of function, regulation and specificity of HOX transcription factors. We are focussing on Drosophila and Human HOX factors. The Drosophila HOX factors have well-defined biological roles and are ideal systems to explore the molecular basis of their function and regulation. The Human HOX factors, on the other hand, are important therapeutic targets for cancer treatment. The longer range translational goals of this research are to help enable diagnostic and therapeutic strategies for HOX related cancers.

Protein Engineering: The current project is concerned with engineering of intein proteins. Protein splicing is a unique post-translational process that involves the excision of an intervening sequence (intein) from a precursor protein, resulting in the ligation of the flanking sequences (exteins) into a single polypeptide chain. This project uses solution NMR spectroscopy and other biophysical methods to dissect the structural and dynamic basis of intein function. The overall goal of this project is to utilize these structural and dynamic studies to engineer intein proteins for novel applications. We are focussing on two specific applications:

1) design of split inteins with minimal cross reactivity with other split inteins;
2) design of highly specific proteases with minimal undesired cleavage at cryptic sites.
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We are using computational methods guided by my NMR studies to design truncation and mutation, followed by synthesis and characterization of the designed proteins.

Publications

Researchgate Profile     Google Scholar Profile
Publications from IIT Kharagpur

1. Analysis of structure and dynamics of intrinsically disordered regions in proteins using solution NMR methods (2021) Nikita V Saibo, Snigdha Maiti, Bidisha Acharya, Soumya De* Book: Advances in Protein Molecular and Structural Biology Methods. [fulltext]
2. Identification of potential short linear motifs (SLiMs) in intrinsically disordered sequences of proteins by fast time-scale backbone dynamics (2021) Snigdha Maiti, Soumya De* Journal of Magnetic Resonance Open. [fulltext]
3. Structural and dynamic studies of the human RNA binding protein RBM3 reveals the molecular basis of its oligomerization and RNA recognition (2021) Sayantani Roy*, Soumendu Boral, Snigdha Maiti, Tushar Kushwaha, Aditya J Basak, Woonghee Lee, Amit Basak, Shivajirao L Gholap, Krishna K Inampudi, Soumya De* The FEBS Journal. [fulltext]
4. Enhancement of angiogenin inhibition by polyphenol‐capped gold nanoparticles (2021) Atashi Panda, Siddhant Karhadkar, Bidisha Acharya, Anwesha Banerjee, Soumya De, Swagata Dasgupta Biopolymers. [fulltext]
5. Structural, Dynamic, and Functional Characterization of a DnaX Mini-intein Derived from Spirulina platensis Provides Important Insights into Intein-Mediated Catalysis of Protein Splicing (2020) Soumendu Boral, Snigdha Maiti, Aditya J. Basak, Woonghee Lee, Soumya De* Biochemistry. [fulltext]
6. Characterization of active/binding site residues of peptidyl-tRNA hydrolase using biophysical and computational studies (2020) Rajkumar Kulandaisamy, Tushar Kushwaha, Vikas Kumar, Soumya De, Saroj Kumar, Santosh Kumar Upadhyay, Manoj Kumar, Krishna K Inampudi International journal of biological macromolecules. [fulltext]
7. Structural Insights into N-terminal IgV Domain of BTNL2, a T Cell Inhibitory Molecule, Suggests a Non-canonical Binding Interface for Its Putative Receptors (2020) Aditya Basak, Snigdha Maiti, Anita Hansda, Dhrunajyoti Mahata, Kheerthana Duraivelan, Shankar Kundapura, Wonghee Lee, Gayatri Mukherjee*, Soumya De*, Dibyendu Samanta* Journal of Molecular Biology. [fulltext]
8. Molecular Details of A Salt-Bridge and Its Role in Insulin Fibrillation by NMR and Raman Spectroscopic Analysis (2020) Bhisma N Ratha, Rajiv Kumar Kar, Zuzana Bednarikova, Zuzana Gazova, Samuel A Kotler, Sreyan Raha, Soumya De, Nakul Chandra Maiti, Anirban Bhunia The Journal of Physical Chemistry B. [fulltext]
9. Dynamic Studies on Intrinsically Disordered Regions of Two Paralogous Transcription Factors Reveal Rigid Segments with Important Biological Functions (2019) Snigdha Maiti, Bidisha Acharya, Veda Sheersh Boorla, Bharat Manna, Amit Ghosh, Soumya De* Journal of Molecular Biology. [fulltext]
10. Structural characterization of VapB46 antitoxin from Mycobacterium tuberculosis : insights into VapB46 – DNA binding (2018) Madhurima Roy, Anirban Kundu, Anirban Bhunia, Sujoy Das Gupta, Soumya De*, Amit Kumar Das* The FEBS Journal. [fulltext]
11. Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway (2016) Carolyn L Fisher, Ross J Resnick, Soumya De, Lucila A Acevedo, Kun Ping Lu, Frank C Schroeder, Linda K Nicholson Journal of Alzheimer's Disease. [fulltext]

Publications from Postdoctoral, PhD and MSc research

• Autoinhibition of ETV6 DNA binding is established by the stability of its inhibitory helix (2016) Soumya De, Mark Okon, BarbaraJ Graves and Lawrence P McIntosh. Journal of Molecular Biology. [fulltext]
• The Modular Structure of the Inner-Membrane Ring Component PrgK Facilitates Assembly of the Type III Secretion System Basal Body (2014) Julien RC Bergeron, Liam J Worrall, Soumya De, Nikolaos G Sgourakis, Adrienne H Cheung, Emilie Lameignere, Mark Okon, Gregory A Wasney, David Baker, Lawrence P McIntosh and Natalie CJ Strynadka Structure.
• Structural characterization of the C3 domain of cardiac myosin binding protein C and its hypertrophic cardiomyopathy-related R502W mutant (2014) XL Zhang, Soumya De, Lawrence P McIntosh and Mark Paetzel Biochemistry. [fulltext]
• Steric mechanism of auto-inhibitory regulation of specific and non-specific DNA binding by the ETS transcriptional repressor ETV6 (2014) Soumya De, Anson CK Chan, H Jerome Coyne, Niraja Bhachech, Ulrike Hermsdorf, Mark Okon, Michael EP Murphy, Barbara J Graves, Lawrence P McIntosh Journal of Molecular Biology. [fulltext]
• TCR scanning of peptide/MHC through complementary matching of receptor and ligand molecular flexibility (2014) William F Hawse, Soumya De, Alex I Greenwood, Linda K Nicholson, Jaroslav Zajicek, Evgenii L Kovrigin, David M Kranz, K Christopher Garcia, Brian M Baker. The Journal of Immunology.
• Complete thermodynamic and kinetic characterization of the isomer-specific interaction between Pin1-WW domain and the amyloid precursor protein cytoplasmic tail phosphorylated at Thy668 (2012) Soumya De, Alexander I Greenwood, Monique J Rogals, Evgenii L Kovrigin, Kun P Lu and Linda K Nicholson Biochemistry. [fulltext]
• Autoinhibition of ETV6 (TEL) DNA binding: appended helices sterically block the ETS domain (2012) Harold J Coyne, Soumya De, Mark Okon, Shaun M Green, Niraja Bhachech, Barbara J Graves and Lawrence P McIntosh Journal of Molecular Biology. [fulltext]
• Putting a Stop to l,d-Transpeptidases (2012) Soumya De and Lawrence P McIntosh Structure.
• Complete determination of the Pin1 catalytic domain thermodynamic cycle by NMR lineshape analysis (2012) Alexander I Greenwood, Monique J Rogals, Soumya De, Kun P Lu, Evgenii L Kovrigin and Linda K Nicholson Journal of Biomolecular NMR. [fulltext]
• Structural biology: The twist in Crk signaling revealed (2010) Linda K Nicholson and Soumya De Nature Chemical Biology.
• Elucidation of a pH-folding switch in the Pseudomonas syringae effector protein AvrPto (2009) Jennifer E Dawson, Jolita Šečkutė, Soumya De, Samuel A Schueler, Aaron B Oswald and Linda K Nicholson Proceedings of the National Academy of Sciences.
• 3'-N-Alkylamino-3'-deoxy-ara-uridines: A new class of potential inhibitors of ribonuclease A and angiogenin (2006) Tushar K Maiti, Soumya De, Swagata Dasgupta and Tanmaya Pathak Bioorganic & Medicinal Chemistry.
• A docking interaction study of the effect of critical mutations in ribonuclease a on protein‐ligand binding (2005) Sayan Mukherjee, Soumya De, Zhumur Ghosh and Swagata Dasgupta Biochemistry and Molecular Biology Education.

Lab members

PhD Scholars (JRF and SRF):

• Bidisha Acharya
• Snigdha Maiti
• Aditya J Basak
• Atashi Panda
• Nikita V Saibo
• Soumendu Boral
• Rituparna Saha
• Aakanksha
• Soumya Sarathi Ganguly
• Rushali Kamath

Undergraduate Students:

• Arpita Sahoo (Biotechnology Department, IIT Kharagpur)
• Ashwin Balaji (Chemistry Department, IIT Kharagpur)
• Srijon Sen (Integrated MSc-PhD in Chemical & Molecular Biology, IIT Kharagpur)

Lab Alumni:

• Vedasheesh Boorla (PhD student, Penn State University)
• Shayan Sarkar (PhD student, Stony Brook University)
• Dilmehak Kaur

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