Start date: 1 September 2022
Large scale functional genomics screens using genome-wide CRISPR screens have enabled the identification of cancer-specific vulnerabilities or “synthetic lethalities” (SLs) at an unprecedented scale. These SLs are the starting points for potentially highly effective novel treatment strategies. To date, the majority of these analyses have focussed on identifying SLs linked to genomic events (primarily mutations); however, recent data from our groups at QUB and UCD indicate that gene and/or protein expression analyses provide an alternative, improved route to the identification of context-specific vulnerabilities (Lord, Quinn & Ryan 2020, Wappett et al. 2021).
Despite significant progress in our understanding of genetic/molecular subgroups of Colorectal cancer (CRC), 5-Fluororuacil (5FU) based-chemotherapeutic regimens remain Standard-of-Care (SoC) for the vast majority of CRC patients. In order to leverage functional genomics approaches to improve treatment of colorectal cancer, our group is performing unique CRISPR-SoC Drug combination screens in human CRC cell lines, with matched gene-expression, epigenetic and proteomic profiling, which will enable genome-wide identification of SoC treatment-induced vulnerabilities.
Building upon our novel analysis methodologies, our expertise in CRC and these unique datasets, this project aims to:
1) Use existing software tools to identify basal and SoC-induced vulnerabilities in molecularly defined CRC sub-groups.
2) Develop novel methodologies and data analysis pipelines for identification of drug-induced effects on gene expression and identification of vulnerabilities this imposes on CRC cells
3) Identify clinically-tractable patient population and relevant models for pre-clinical validation of predictions.
4) Develop a Public “Shiny” interface for analysis and sharing of this data with the scientific/clinical community.
Embedding of the student within the colorectal cancer research cluster in QUB, through which the student will have access to unique expertise and extensive highly curated/annotated clinical datasets with Multi-Omic data (e.g. Allen Et al. 2018) as well as other pre-clinical genomics datasets in human and mouse models of CRC to achieve the project goals. The student will benefit from the supervisory team’s expertise in genomics and methods for analysing CRISPR screen data and their strong international collaborative networks; as well as complementary expertise in the analysis of transcriptional and epigenomic data (McDade QUB), machine, deep-learning (O’Broin NUIG) synthetic lethality and analysis of proteomic data (Ryan UCD), which will include a visits and/or periods of work at both the O’Broin and Ryan labs.
Queen’s University Belfast is a partner of the SFI CRT in Genomics Data Science, which was formed in 2019. Over seven years of its operation, the Centre will train 100 PhD students in data analytical and computational skills that will help power the implementation of genomics on the island of Ireland. The Centre is built on a national cohort-based model of advanced training. At the outset of their training programme, each student cohort undertakes an intensive, semester-long series of training courses. Participation in the SFI CRT in Genomics Data Science includes a mandatory 3-month residential training programme for the students at NUI Galway, held in Semester 1 (start of September to mid-December) of Year 1 of the PhD programme. Through their experience of working and living together on this phase of the training programme, student cohorts form tight knit groups, enabling them to work collectively on the data science challenges they will encounter during their research. For more information on the SFI CRT in Genomics Data Science and the residential training programme see: https://genomicsdatascience.ie/
Students would benefit from having some experience with bioinformatics / computational biology tools and analyses, although training in these areas will be provided in the residential training programme at the start of the project.
Further funding eligibility: ROI (and EU applicants with pre-settled/settled) status may be eligible for funding if 3 year UK residency met.
You must hold or expect to get an upper second class honours degree from a university in the UK or Ireland, or qualifications and experience considered by the University as equivalent to that standard. Candidates who already hold a doctoral degree, or who have registered on a PhD for one year (or part-time equivalent) or not eligible.
Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.
The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
· IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
· TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
· A valid Certificate of Proficiency in English grade A or B;
· A valid Certificate of Advanced English grade A; or
· A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.
For a list of English Language qualifications also accepted by the School and University please see the following link:
INTO Queen’s English Language Courses offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained at: https://www.qub.ac.uk/International/International-students/Applying/University-Preparation-Courses/INTOEnglishlanguagecoursesatQueens/