Discoverybytes
Co-localization of signaling molecules to a stable cell-cell interface is a key prerequisite for signaling in systems such T cell activation.
Core trick
Derives receptor co-localization from bispecific geometry parameters and ranks single-pass membrane receptor pairs by a composite opportunity score.
Description
Co-localization of signaling molecules to a stable cell-cell interface is a key prerequisite for signaling in systems such T cell activation. We had previously built a model that indicated bifunctional antagonists, such as bispecific antibodies, might have unexpected activating function in such systems.
We revisited the concept to do the following.
1. Confirm the math behind the model and build a user-friendly interface to visualize activation / inhibition
2. Generate a table of receptor proteins that span the cell membrane once, and are involved in signaling. These are candidate targets for modulation via this co-localization mechanism of action.
3. Expand the candidate target data to include data for interaction partners, disease associations (including rare/orphan), therapeutic objective (i.e. activate/inhibit), highest drug clinical stage for any targeting the receptor. We ranked pairs by a composite Opportunity Score, then narrowed to three rare/orphan diseases with clean ligand-replacement logic: CD70-CD27 (severe combined immunodeficiency), DLL4-NOTCH1 (Adams-Oliver syndrome), and EDA-EDAR (hypohidrotic ectodermal dysplasia).
DLL4-NOTCH1 lacks a disease-modifying option, making it our lead despite highest mechanistic risk: Notch activation requires active endocytic force, not proximity alone.
Molecular design concept would tether a nanobody against EFNB2, an endothelial protein coupled to Notch signaling, to one against NOTCH1.
discoverybytes/built-with-claude-life-sciences★ 00 forksHTMLMITCreated Jul 7, 2026 · last push Jul 12, 2026
README excerpt
# Receptor Co-localization at Cell–Cell Interfaces under Bispecific Engagement > Assessing the effect of bispecific antibodies, antibody–drug conjugates (ADCs), > and bispecific molecules on the co-localization / enrichment of receptors at > cell–cell interfaces. **Built with Claude — Life Sciences (Research Track).** --- ## Scientific question Does engagement by a bispecific molecule drive measurable co-localization of the targeted receptors at the cell–cell interface, and how does that depend on the molecule's architecture (valency, geometry, affinity/avidity)? *(Full working hypothesis and running scientific record are in [`notebook/LAB_NOTEBOOK.md`](notebook/LAB_NOTEBOOK.md).)* ## Status Model reimplementation, figure reproduction, an architecture-sweep co-localization metric, and an independent robustness check are complete. See [`notebook/LAB_NOTEBOOK.md`](notebook/LAB_NOTEBOOK.md) (Entries 1-3) for the full chronological record. ## Source material This project reimplements and stress-tests the closed-form receptor co-localization signaling model from: > Proudfoot, J. *Non-selective antagonists acting at a stable cell-cell > interface have the potential to induce signaling.* ChemRxiv (2024). > https://doi.org/10.26434/chemrxiv-2024-9kfl4 which models signal arising from receptor A / co-receptor B co-localization at a stable cell-cell interface using receptor-occupancy theory (Stephenson, *Br J Pharmacol Chemother* 1956), and predicts that a non-selective bif