Overview
The Bhattacharyya Lab employs an integrative approach to understand the molecular mechanism for the regulation and activation of kinase signalling pathways in the context of learning and memory, and cognitive impairments in Down Syndrome.
Overview
The Bhattacharyya Lab employs an integrative approach to understand the molecular mechanism for the regulation and activation of kinase signalling pathways in the context of learning and memory, and cognitive impairments in Down Syndrome.
Overview
The Bhattacharyya Lab employs an integrative approach to understand the molecular mechanism for the regulation and activation of kinase signalling pathways in the context of learning and memory, and cognitive impairments in Down Syndrome.
The hattacharyya Lab
Preserve biological complexity. Achieve molecular resolution.
Revealing how nanoscale organization of membrane proteins translates to cellular signaling in health and disease.
1
Nanoscale Organization
What does a signaling complex look like in its native environment?
Our Native-nanoBleach approach captures ~10 nm circular patches of native membrane to determine native oligomeric distribution of membrane protein complexes.
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Works at endogenous expression levels of target membrane proteins
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No detergents or crosslinkers
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Resolves stoichiometry and heterogeneous oligomeric distributions at single molecule level
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Effective lateral spatial resolution of ~10 nm
Key Focus: Stoichiometry, Heterogeneity, Dynamics
PMID: 38012273
BioRxiv: 10.1101/2023.02.19.529138
2
Receptor Signaling
How can the same receptor bind different ligands to produce different biological outcomes?
Using a painless NGF variant, we uncoupled TrkA downstream neurotrophic and nociceptive signaling.
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Reduced PLCγ1 pathway activation, preserved ERK and AKT signaling
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Lower dimer/oligomer formation
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Less TRPV1 sensitization
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Supported by cryo-EM, biochemistry, SPT, and electrophysiology
Key Focus: TrkA, TAM receptors,
Bias & specificity
PMID: 41332679
BioRxiv: 10.1101/2025.11.18.686377
3
Lipid Regulation
How do lipids control where and when signaling proteins act?
We used native MS and lipidomics to define lipid environments and linked them to kinase activity. Our PNAS 2026 study on BTK revealed a two-step activation mechanism:
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Abundant phosphatidylserine (PS) first recruits BTK to the membrane
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BTK then efficiently encounters the rare lipid PIP3 and becomes activated
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PS sensitizes BTK for activation by PIP3
Key Focus: Protein-lipid interactions, Lipidomics, Mechanism
PMID: 42372161
DOI: 10.1101/2025.10.28.685231
4
Membrane Contact Sites
How do organelles communicate across nanoscale interfaces?
We develop native approaches that capture two interacting membranes together with the protein complexes that bridge them.
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Capture native organelle interfaces
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Detergent-free, dual-membrane preservation
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Determine composition and stoichiometry
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Reveal architecture and heterogeneity
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Connect to lipid transfer and Ca2+ signaling
Key Focus: ER-mitochondria, nuclear envelope, ER-plasma membrane