Identification of novel vulnerabilities in cancer cells
In most -if not all- forms of cancer, large portions of chromosomes have been lost, particularly areas of the genome that contain tumor suppressor genes. In addition to these tumor suppressor genes, their flanking genes are also lost. Loss of these genes is often referred to as 'passenger mutations', which are mutations that are often in cancer cells but that do not affect cancer growth and survival (as opposed to 'driver' genes, which are essential for cancer progression). While these passenger mutations do not affect cancer growth, the loss of these genes often does make the cancer cell highly dependent upon the remaining copy of that allele on the corresponding non-mutated chromosome. This may represent a vulnerability, because blocking the remaining copy of the gene can lead to rapid cancer cell death (often referred to as synthetic lethality). This form of synthetic lethality has remained little explored for development of novel cancer treatment.
The goal of this project is to discover passenger mutations that can be exploited for development of novel cancer treatment.
The first aim is to assemble a compendium of passenger genes that are often lost in cancer cells. This involves the use of bioinformatics to 'mine' cancer databases, such as the Cancer Genome Atlas. We will determine which parts of chromosomes are commonly lost in specific forms of cancer. Next, we will study these chromosomal areas to see which genes encode 'druggable targets', i.e. genes that encode enzymes that can be inhibited by small molecule inhibitors. We will then test whether cancer cells are indeed hypersensitive to these inhibitors. The results will also be validated using CRISPR/Cas9 technology.
What we offer the student
- Experience with bioinformatics and datamining
- Experience with cancer cell genetics
- Experience in molecular biology and biochemistry methods, including Western blotting, PCR, RT-qPCR.
- Training in transferrable skills: presentations, writing, project planning
- You get to be part of an international research team with researchers at different stages of their careers
- Frequent opportunities to get input on your data (weekly lab meetings and weekly 'hypothesis testing discussions' with the PI) and to get updated on the most recent advances in our field of interest (“journal club” presentations)
- Participation in annual CanCell Centre of Excellence meetings with the opportunity to present your data in a poster session
- The possibility to interact with cancer patient representatives through our user panels
- We have an ambitious, yet very positive and friendly working environment where team members share their expertise to help each other get better!
Our research group
The “Cancer Molecular medicine” research group is led by Jorrit Enserink and consists of 12 members from 6 different countries. One of our research areas is leukemia and the development of new therapies for AML patients. The group is a young and dynamic environment and has long experience in supervision of master- and PhD students (five successful MSc degrees in 2019 alone). Our group is part of the Department for Molecular Cell Biology at Radiumhospitalet, where we share facilities, reagents and expertise with other groups on a wide variety of models. We are also part of the CanCell Centre of Excellence.