This AI-Ready Single-Molecule Proteomics $1.6M Grant Targets Parkinson’s Alpha Synuclein
Washington- and California-based Nautilus Biotechnology is teaming up with Weill Cornell Medicine–Qatar and the Michael J. Fox Foundation (MJFF) for Parkinson’s Research on a new research program targeting alpha-synuclein, a protein that studies suggest may be a critical driver of Parkinson’s disease pathogenesis.
The effort, supported by a $1.6 million MJFF grant, also aims to create a new single-molecule assay capable of precisely detecting different “proteoforms” of this protein—variants that could serve as early biomarkers for disease onset and progression.
Alpha-synuclein is associated with Parkinson’s pathology, but it doesn’t exist in just one form. It appears in many subtly altered versions—such as ones that are truncated or chemically modified by so-called post-translational modifications (PTMs) after being made in cells. These many different proteforms may help explain how the disease develops and varies from person to person, but current tools are often too crude to measure them individually and at scale.
The collaboration combines three capabilities:
- Nautilus’ single-molecule proteomics platform and Iterative Mapping technique, designed to analyze billions of intact proteins at the single-molecule level in parallel and resolve differences missed by bulk methods.
- Weill Cornell–Qatar’s custom-made protein standards and reagents, built in Hilal Lashuel’s lab, which has a long track record of studying alpha-synuclein PTMs.
- MJFF’s focus on advancing molecular biomarkers to support earlier diagnosis and tailored treatment approaches for Parkinson’s.
The goal is to quantify a broad set of alpha-synuclein proteoforms with enough resolution to make them useful as clinical indicators. If successful, the work could enable more accurate patient stratification, monitor disease activity, and inform therapeutic development across synucleinopathies.
The program follows similar efforts by Nautilus in Alzheimer’s disease, where it’s applying its platform to study tau protein variants through partnerships with the Buck Institute and the Allen Institute. Earlier this month, the company also launched an Early Access Program to bring its single-molecule platform closer to commercialization.
Nautilus’ proteome analysis platform is built around Iterative Mapping, which allows billions of intact proteins to be analyzed in parallel at the single-molecule level. Using ultra-dense arrays, repeated probing steps, and machine learning-powered algorithms, the system identifies each protein molecule and delivers accurate, sensitive, and reproducible quantifications by summing all molecules with the same identity.
These are then decoded using machine learning to identify and quantify proteins with high precision and reproducibility. The platform is designed to scale to full-proteome coverage, integrate easily into lab workflows, and produce standardized datasets suitable for AI-based analysis.
Nautilus recently published a preprint demonstrating how its single-molecule platform and Iterative Mapping method can be applied to complex disease targets, with initial validation shown in tau protein analysis.
Topic: AI in Bio
