Research

Designing and characterization of antimicrobial peptides (AMPs) and their applications in the agriculture and healthcare sectors

Designing improved Pharmacokinetic therapeutics and Transgenic Plants with Enhanced Innate Immunity

Our lab focuses on comprehensive studies of de novo-designed antimicrobial peptides (AMPs), correlating their structure and function in treating plant diseases. Efforts are in full swing to develop, a transgenic plant, over-expressing the desired AMP using an Agrobacterium-based binary vector system. Alternatively, these peptides have been studied for their potency in efficiently combating sepsis and neutralizing it.
Selected Publications:
Datta A, Ghosh A, Airoldi C, Sperandeo P, Mroue KH, Barbero JJ, Kundu P, Ramamoorthy A, Bhunia A* (2015) Antimicrobial peptides: Insight into Membrane Permeabilization, Lipopolysaccharide Fragments and Application in Plant Disease Control. Nature Sci. Rep., 5, 11951.
Datta A, Bhattacharyya D, Singh S, Ghosh A, Schmidtchen A, Malmsten M*, Bhunia A* (2016) Role of Aromatic Amino Acids in Lipopolysaccharide and Membrane Interactions of Antimicrobial Peptides for Use in Plant Disease Control. J. Biol. Chem. 291, 13301 - 17
Datta A, Kundu P, Bhunia A* (2016) Designing potent antimicrobial peptides by disulphide linked dimerization and N-terminal lipidation to increase antimicrobial activity and membrane perturbation: Structural insights into lipopolysaccharide binding. J. Colloid Interface Sci., 461, 335-345
Chowdhury R, Ilyas H, Ghosh A, Ali H, Ghorai A, Midya A, Jana NR, Das SS,* Bhunia A* (2017) Multivalent Gold nanoparticle - Peptide Conjugates for Targeting Intracellular Bacterial Infection. Nanoscale 9(37), 14074-14093.

Nanoparticle-conjugated Therapeutic Designing and Drug Delivery

Recently, we have started working on nano-particles, quantum dots, cell-penetrating peptides (CPP), or PEG conjugation for improved drug delivery to specific microbial targets or sites in the mammalian tissue including the Central Nervous System, against the tight junctions of the Blood-Brain Barrier (BBB).

Selected Publications:

Bera S, Kar RK, Mondal S, Pahan K, Bhunia A* (2016) Structural Elucidation of Cell-Penetrating Penetratin Peptide in Model Membranes at Atomic Level : Probing Hydrophobic Interactions in the Blood-Brain-Barrier. Biochemistry 55, 4982-4996

Mohid SA, Ghorai A, Ilyas H, Mroue KH, Narayanan G, Sarkar A, Ray SK, Biswas K, Bera AK, Malmsten M*, Midya A*, Bhunia A* (2019) Application of Tungsten Disulfide Quantum Dot-Conjugated Antimicrobial Peptides in Bioimaging and Antimicrobial Therapy. Colloids and Surfaces B: Biointerfaces 176, 360-370.

Patel KD, Mohid SA, Datta A, Aricthota S, Bhunia A, Haldar D, Sarojini V* (2021) Synthesis and Antibacterial Study of Cell-Penetrating Peptide Conjugated Trifluoroacetyl and Thioacetyl Lysine modified Peptides European Journal of Medicinal Chemistry 219: 113447.

Ilyas H, van der Plas M, Agnoletti M, Kumar S, Mandal AK, Atreya HS, Bhunia A*, Malmsten M* (2021) Effect of PEGylation on Host Defence Peptide Complexation with Bacterial Lipopolysaccharide Bioconjugate Chemistry

Herbolomics – A research front for Sustainable Future

A current interest of the lab is in screening of natural compounds as potential targetted therapeutics. Most of these compounds have been integral to traditional medical practices however has not been explored for their specificity against progressive amyloidosis. In our recent studies we have been screening for extracts to identify, investigate and repurpose them as effective therapeutics against amyloid beta (β) aggregates. We employ high resolution NMR spectroscopy along with microscopy and cell biology to analyze the mechanism of inhibition and their efficiciency in vitro. These comprehensive screening studies are aimed to encourage and promote studies in vivo.
Selected Publications:

Pariary R, Shome G, Dutta T, Roy A, Misra AK, Jana K, Rastogi R, Senapati D, Mandal AK, Bhunia A* (2024) Enhancing Amyloid Beta Inhibition and Disintegration by Natural Comounds: A Study Utilizing Spectroscopy, Microscopy and Cell Biology Biophysical Chemistry Just accepted (invited article for a special issue).

Understanding amyloidogenesis in the pathophysiological scenario of several metabolic disorders.

We have reported the early transient conformers of α-synuclein in Parkinson’s disease etiology and the atomic resolution characterization of the stepwise nucleation events in amyloid β. Focus at the functional interface of membranes has provided us with a more realistic and reasonable structural and dynamic state of the functional conformers, underlying the pathophysiological conditions. These preliminary studies have helped us to design and develop novel small molecules or peptides (or peptidomimetics) against the specific structural motifs for the efficient inhibition of the oligomerization events.

Probing the Functional Interface of Biomembranes

Our studies have been characterizing the dynamics of residue-specific membrane interaction of several of the biologically active AMPs and amyloid peptides/proteins, having employed model membrane mimicking systems, e.g., micelles, bicelles or liposomal vesicles (SUVs, LUVs, and GUVs). Currently, our laboratory is working on nanodisc lipid systems that are more stable and structurally better.

Selected Publications:

Bera S, Korshavn KJ, Kar RK, Lim MH, Ramamoorthy A, Bhunia A* (2016) Biophysical Insights into the Membrane Interaction of the Core Amyloid Forming Ab40 Fragment K16-K28 and its Role in the Pathogenesis of Alzheimer's Disease. Phys Chem Chem Phys. 18, 16890-901.

Pal I, Bhattacharyya D, Kar RK, Zarena D, Bhunia A*, Atreya HS* (2019) A Peptide-Nanoparticle System with Improved Efficacy against Multidrug-Resistant Bacteria.

Ghosh A, Bhattacharyya D, Bhunia A* (2018) Structural Insights of a Self-assembling 9-Residue Peptide from the C-terminal tail of the SARS Corona Virus E-protein in DPC and SDS Micelles: A Combined High and Low Resolution Spectroscopic Study BBA - Biomembrane 1860, 335-346.

Ratha BN, Kim M, Sahoo B, Garai K, Lee D-K, Bhunia A* (2018) Insulin-Eukaryotic Model Membrane Interaction: Mechanistic Insight of Insulin Fibrillation and Membrane Disruption. BBA - Biomembrane pii: S0005-2736(18)30049-X.

Bhattacharyya D, Kim M, Mroue KH, Park MS, Tiwari A, Saleem M, Lee D-K*, Bhunia A* (2019) Role of Non-electrostatic forces in Antimicrobial Potency of a Dengue-virus derived fusion peptide VG16KRKP: Mechanistic insight into the interfacial peptide-lipid interactions. BBA 1861, 798-809

Bera S, Gayen N, Mohid SA, Bhattacharyya D, Krishnamoorthy J, Sarkar D, Choi J, Sahoo N, Mandal AK, Lee D, Bhunia A* (2020) Comparison of Synthetic Neuronal Model Membrane Mimics in Amyloid Aggregation at Atomic Resolution. ACS Chem Neurosci 11(13): 1965-77

Trapping the Invisible Dynamic States

Our recent solution-state NMR studies suggest a necessary shift in focus from the definite conformers to the dynamic ones that are the most toxic in terms of their functionality. The application of a multitude of state-of-the-art novel experiments, including the newly developed saturation transfer-based technique, DEST (Dark-state Exchange Saturation Transfer) NMR, has enabled us to gain access to the “dark” or "invisible" dynamic intermediate conformers. This has provided a high-resolution structural correlation to protein function.

Selected Publications:

Bhattacharyya D, Kumar R, Mehra S, Ghosh A, Maji SK*, Bhunia A* (2018) Multitude NMR Studies of alpha-Synuclein Familial Mutants: Probing their Differential Aggregation Properties. Chemical Communications 54, 3605-3608.

Brender JR, Ghosh A, Kotler SA, Krishnamoorthy J, Bera S, Morris V, Sil TB, Garai K, Reif B, Bhunia A*, Ramamoorthy A* (2019) Probing Transient Non-Native States in Amyloid Beta Fiber Elongation by NMR. Chemical Communications 55, 4483 - 86

Bhattacharyya D, Mohite GM, Krishnamoorthy J, Gayen N, Mehera S, Navalkar A, Kotler SA, Ratha BN, Ghosh A, Kumar R, Garai K, Mandal AK, Maji SK, Bhunia A* (2019) Lipopolysaccharide from Gut Microbiota Modulates Alpha-Synuclein Aggregation and Alters its Biological Function. ACS Chemical Neuroscience 10(5), 2229-36.

Sarkar D, Chakraborty I, Condorelli M, Ghosh B, Mass T, Weingarth M, Mandal AK, La Rosa C*, Subramanian V*, Bhunia A* (2020) Self-assembly and Neurotoxicity of Amyloid-beta (21-40) Peptide Fragment: The Regulatory Role of GxxxG Motifs. ChemMedChem 15(3), 293-301.

SARS-CoV Envelope protein

The coronavirus E protein plays essential roles in virion assembly, budding, morphogenesis, and regulation of other cellular functions. Our current research aims to adopt a multidisciplinary approach combining high-resolution NMR spectroscopy with bioinformatics and molecular biology to identify specific functional target sequences for efficient therapeutic strategies.

Selected Publication:

Ghosh A, Pithadi A, Bhat J, Bera S, Midya A, Fierke C, Ramamoorthy A, Bhunia A* (2015) Self-assembly of a 9-residue amyloid-forming peptide fragment of SARS Corona Virus E-protein: Mechanism of self aggregation and amyloid inhibition of hIAPP. Biochemistry, 54, 2249 -2261

Mukherjee S, Bhattacharyya D, Bhunia A* (2020) Host-Membrane Interacting Interface of the SARS Coronavirus Envelope Protein: Immense Functional Potential of C-terminal Domain. Biophys Chem 266: 106452.

Mukherjee S, Harikishore A, Bhunia A* (2021) Targeting C-terminal Helical bundle of NCOVID19 Envelope (E) protein. International Journal of Biological Macromolecules 175: 131-139

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