The “Proteus” CRISPR System and the Undergraduate Student Leadership Behind It

A team of passionate undergraduate researchers has been awarded Centre de Recherche en Biologie Structurale (CRBS) Blue Sky Seed Funding to pursue an exciting CRISPR-based cancer treatment. Their project, progressing in collaboration with investigator Logan Walsh at the Rosalind and Morris Goodman Cancer Institute (GCI) and CRBS investigator Maureen McKeague, centres around a CRISPR-based system called “Proteus”. This undergraduate led initiative was developed at McGill and won the Grand Prize at the 2023 iGEM Grand Jamboree – the top world-wide student competition in synthetic biology.

The Science Behind Proteus: Genetic-based Precision Medicine

The Proteus system builds upon CRISPR technology, designed to induce cell death specifically in cancer cells carrying oncogenic mutations, while leaving healthy cells untouched. The first step of the approach employs the hybrid protein Craspase: one component activates on recognition of the target mutation, and the rest of the protein cleaves target proteins. Once Craspase identifies mutations in cancer cells, it activates the second step of the system by cleaving engineered proteins and triggering them to induce cell death.

By being able to differentiate between tiny genetic differences that separate healthy from cancerous cells and vary from patient to patient, Proteus could be a highly targeted cancer therapy. While many current cancer treatments damage healthy tissue alongside malignant cells and cause toxic side effects, the precision of Proteus is a major leap forward.

Student Leadership: The Drive Behind Proteus

An exciting aspect of the Proteus project is that it is entirely driven by undergraduate students. The team, who initially developed the idea for the 2023 iGEM Grand Jamboree, includes Albert Nitu, Elliot Cole, Emily Martin, Jonas Lehar, Megan Farrow, Mia Bhatia, and Owen Tang. Reflecting on the experience of leading a research team, Albert shared, “Bringing together a research team, establishing the project’s vision and leading its design and experimental work, as well as setting up interdisciplinary research collaborations has been such a unique and valuable learning experience”.

The Next Chapter for Proteus: Idea to Implementation

The results for Proteus have been promising in yeast models - the next step, made possible by the CRBS Blue Sky Seed Funding, will allow the team to test Proteus in human cancer cells. Securing this funding gave the team a crucial boost, allowing them to move from preliminary experiments to investigating clinical relevance for use in personalized cancer treatments.

"By far the most rewarding part of this project has been turning it from an idea on a whiteboard into a working system in the lab," Albert explained. This sense of ownership and achievement underscores the uniqueness of this initiative - students have led every stage of the research process, from conceptualization to preliminary data generation. With CRBS Blue Sky Seed Funding, they are now set to take the next big step and bring this therapy closer to patients.