Understanding the telomere length maintenance mechanisms in pancreatic cancer

Deadline for applications has passed.

Key information

Applications closed
06 February 2024, 11:59 GMT
Hours per week
36 (full time)
Application guidance
Posted 22 December 2023

Research topics

Tumour Biology Genome Integrity & Repair Cell Biology
Background texture taken from the lab imagery.

This is a summer student position supervised by Ronnie Low in Simon Boulton's lab.

Introduction to the Science

Pancreatic cancer remains one of the most lethal cancers to-date. Pancreatic cancer can arise from different cellular origins into two major types: pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET). To achieve indefinite replication, pancreatic cancer cells have evolved telomere maintenance mechanisms (TMMs), including telomerase and alternative lengthening of telomere (ALT). Activation of TMMs prevent telomeres from undergoing catastrophic shortening, which ultimately leads to cell cycle arrest or cell death. Recent genomic studies in pancreatic cancer patients (reference 1) suggested that PDAC and PNET utilise different TMMs to achieve cellular immortality. However, the mechanism behind this differential TMM regulation in these two related cancers is unknown.

About the Project

The aim of this project is to understand how pancreatic cell types and prevalent genetic mutations can influence TMMs in pancreatic cancer. To study how specific genetic loss affect TMMs, we can perform genetic editing in pancreatic cancer cell lines or in induced pluripotent-stem cell derived organoids. To study the effect of cell types in TMM utilisation, we can also induce a change in cell types (reference 2) either through exposure to cytokines, or exposure to chemotherapeutic agents. We will then perform microscopy-based techniques to investigate the hallmarks of TMMs. In this project, you will learn a range of cell culture, molecular biology, and microscopy techniques to investigate telomere lengthening in pancreatic cancer progression.

About You

This project would suit a student studying molecular biology, biomedical science, or medicine, who has particular interest in understanding the mechanism of cancer biology. The DSB Repair Metabolism group has a broad interest in genome instability research, including DNA damage repair mechanism and telomere biology. So, this is a good project for anyone interested in this field.

References

 

1.         ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium (2020)

            Pan-cancer analysis of whole genomes.

            Nature 578: 82-93. PubMed abstract

2.         Low, R.R.J., Fung, K.Y., Gao, H., Preaudet, A., Dagley, L.F., Yousef, J., . . . Putoczki, T.L. (2023)

            S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer.

            Cell Death and Differentiation 30: 1155-1165. PubMed abstract