Final Project Ideas

FINAL PROJECT IDEAS

  • GXM UPTAKE INHIBITOR (s.neoformans, c.gatti)

  • EARLY LIVER DAMAGE BIOSENSOR

  • BIOSENSOR FOR TOXICOLOGY

GXM UPTAKE INHIBITOR (GXM SHIELD)

Concept: A dual-therapy approach using in silico designed proteins to Shield liver receptors and a non-Fc Sponge to neutralize and redirect GXM to renal clearance.

Aim 1: The Liver Shield (Receptor Antagonism)

Goal: Block the “portals” (CD14, SR-A1, TLR4) that capture GXM into the liver/spleen.

  • Step 1: Interface Mapping: Use AlphaFold 3 to map the hydrophobic pockets of human CD14 (residues 1–152) and the trimeric collagenous domain of SR-A1.

  • Step 2: Design: Generate small, high-affinity protein “plugs” that mimic GXM but lack its toxic signaling.

  • Step 3: Sequence Refinement: Use ProteinMPNN to ensure these binders are highly soluble and stable at physiological pH (7.4).

Primary Toolset: AlphaFold 3, RFdiffusion, ProteinMPNN, PyMOL (visualization).

Aim 2: The GXM Sponge (Non-Fc Sequestration)

Goal: Create a high-affinity “scavenger” protein that binds circulating GXM without triggering liver uptake.

  • Step 1: Epitope Modeling: Model the M2 hexasaccharide motif of GXM (focusing on mannose backbone).
  • Step 2: Binder Generation: Design a scaffold based on the known GXM-binding peptide sequence.

Primary Toolset: BindCraft, AlphaFold 3 (Carbohydrate module), Rosetta (stability testing).

Aim 3: Systems Modeling & Clearance Simulation

Goal: Quantify the therapeutic window and “redirection” efficiency.

  • Step 1: Pharmacokinetic (PK) Modeling
  • Step 2: Competitive Binding Simulation. Simulate the “Shield” occupying 90% of Kupffer cell receptors before the “Sponge” is released.
  • Step 3: Clearance Prediction. Calculate the rate of Renal Clearance vs. Liver Accumulation for the Sponge-GXM complex.

Primary Toolset: PK-Sim, MATLAB (SimBiology), R (mrgsolve).

Experimental Validation (Wet Lab)

  1. Production: Synthesize the Aim 1 & 2 proteins via E. coli expression or mRNA-LNP delivery.
  2. Binding: Confirm the Sponge’s affinity for purified GXM.
  3. Competition: Perform a Flow Cytometry assay on human HepG2 or Kupffer cells to prove the Shield prevents GXM uptake.