Life runs on ribosomes.
Collide Therapeutics is building the first therapies targeting ribosome quality control to treat neurodegeneration and aging, enabling longevity from the most fundamental machinery of life.
A Root Cause, Once Unreachable
“Increased ribosome pausing, leading to RQC overload and nascent polypeptide aggregation, critically contributes to proteostasis impairment and systemic decline during ageing.”Stein et al., Nature 601(7894), 2022
Ribosomes are the most fundamental machines in biology. They execute all protein synthesis and consume the majority of a cell’s energy. Every living organism depends on them, and when they malfunction, the consequences propagate everywhere.
Ribosome quality control (RQC) is the cellular system that detects and resolves ribosomal dysfunction. Its failure drives Alzheimer’s, Parkinson’s, ALS, and the process of aging itself. Current therapeutics target downstream malformed proteins, ignoring the upstream failure. That is why they fail.
Targeting RQC has been impossible: the structural basis of its key regulators eluded complete characterization for over a decade. Collide’s paradigm-defining AI models have solved this problem, opening an entirely new class of therapeutics.
A New Class of Discovery
Collide combines AI-native tooling, automated pipelines, and deep integration with the scientific research ecosystem to move from target to candidate with more speed, cost-effectiveness, and impact. We explicitly target mechanisms and pathways that were previously thought to be intractable.
Models Built for This Problem
Collide develops both custom AI models and open-source pipelines purpose built to surpass decade-long barriers in the field. Our models resolve problems intractable to conventional methods, and our open-source tooling is shared with the broader scientific community.
Scalable by Design
End-to-end automated pipelines span target characterization, compound generation, and lead optimization. A design cycle that once took years now takes days. We automate integration, optimization, and research development of open-source models and tools, enabling unprecedented efficiency.
Part of the Research Commons
We build on a decade of published RQC science and actively contribute back through preprints, open model releases, and community datasets. Collide benefits from the research ecosystem and accelerates it in return.
Lead Programs
CLD-002
ZNF598 Activator
CLD-008
ZNF598 Activator
Built on a Decade of Discovery
The connection between ribosome quality control and neurodegeneration has been established across multiple model systems and disease contexts. Collide’s paradigm-defining AI models have resolved what this body of work left structurally intractable — enabling, for the first time, rational drug design against the RQC pathway. This work is in preparation for submission to Nature Communications.
Altered translation elongation contributes to key hallmarks of aging in the killifish brain
Di Fraia, D. et al.
RQC & aging in vertebrate brain
DOI ↗Single-protein/RNA imaging reveals ZNF598 as a limiting factor in resolving collided ribosomes
De La Cruz, A.C. et al.
Rate-limiting step in RQC
DOI ↗Stalled translation by mitochondrial stress upregulates a CNOT4–ZNF598 ribosomal quality control pathway important for tissue homeostasis
Geng, J. et al.
RQC pathway in tissue homeostasis
DOI ↗ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD
Park, J. et al.
RQC rescues ALS model
DOI ↗Inefficient quality control of ribosome stalling during APP synthesis generates CAT-tailed species that precipitate hallmarks of Alzheimer’s disease
Rimal, S. et al.
RQC failure drives Alzheimer’s pathology
DOI ↗Translation stalling and ribosome collision leading to proteostasis failure: implications for neurodegenerative diseases
Lu, B.
RQC & neurodegeneration review
DOI ↗