Understanding the role of SNHG32 as a regulator of adaptive resistance in lymphoid cancers

About the Project

This project tackles a major challenge in lymphoma treatment: adaptive drug resistance. Building on novel findings linking cancer cell resistance to histone deacetylase inhibitors to the non-coding gene SNHG32, it will uncover how the transcription products of this gene, previously unexplored small nucleolar RNA and long non-coding RNA molecules, affect gene expression and cell behaviour. By revealing new epigenetic mechanisms of resistance, this research could identify innovative therapeutic targets and inspire more effective, durable lymphoma treatments.

Some lymphoma cancer cells can learn how to survive treatments that are meant to destroy them. This ability is called adaptive resistance. Scientists know that changes in genes can help cancer cells do this, but they still do not fully understand other changes that affect how genes are turned on or off, known as epigenetic changes.

Earlier research has shown that when lymphoma cells become resistant to a cancer drug called romidepsin, changes happen in a specific area of DNA called 6p21. One important gene in this area is SNHG32. Our research team has found that when this gene is switched off using a gene-editing tool called CRISPR/Cas9, the cancer cells behave in a similar way to cells that are resistant to romidepsin.

The SNHG32 gene does not make a protein. Instead, it produces three types of RNA molecules that help control how cells work. These are SNORD48, SNORD52, and a longer RNA called SNHG32lncRNA. We do not yet know how these RNA molecules work together or how they help cancer cells survive treatment.

This project aims to find out what each of these RNA molecules does. It will study whether SNORD48 and SNORD52 help protect SNHG32lncRNA and other RNAs, and which molecules SNHG32lncRNA interacts with inside the cell. Overall, this research will help us better understand how lymphoma cells resist treatment and may support the development of improved cancer therapies.

In this project the student will use RNA Antisense Purification to identify DNA, RNA and protein interacting partners of SNORD48, SNORD52 and SNHG32lncRNA. Bioinformatics approaches will be used to predict and validate potential targets, and mechanistic understanding will be probed using RNA degrading techniques such as CRISPR/Cas13.

The student will receive comprehensive, cross-disciplinary training from supervisors, collaborators, and experienced lab members in the specific experimental and computational techniques required for the project, including analysis of generated and archived datasets. They will participate in weekly lab research meetings, presenting their work and engaging in constructive scientific critique. Regular one-to-one meetings with supervisors will support project progress and provide career coaching. Additional development opportunities include seminars, workshops, scientific societies, and national and international conferences. The Institute’s active research and postgraduate community fosters collaboration, while strong emphasis is placed on student wellbeing, mental health awareness, and maintaining a healthy work–life balance.

For further information please contact Professor Joseph Slupsky (email: jslupsky@liverpool.ac.uk). When making application, please use the same contact and email, stating within subject line “Application to NWCR/MABC Robina Crowe PhD Studentship”, and include your CV, cover letter and the names of two professional referees who have knowledge of your academic performance and ability in the laboratory.