An exciting position has become available for a Senior Bioinformatician within the Cancer Genetics department at the Wellcome Trust Sanger Institute.
The Wellcome Trust Sanger Institute has been awarded an ERC Synergy grant to explore the use of combinatorial therapies to overcome drug resistance in cancer, using human cancer cell lines as well as state-of-the-art mouse models. A significant component of this project is the generation and analysis of in vitro models of acquired drug resistance in cancer cell lines and organoids through the use of genome-wide forward genetic screens using a variety of technologies including genome-wide CRISPR/Cas9 screens, chemical and lentiviral vector-based insertional mutagenesis systems. Once drug resistance mechanisms are identified, we will employ high-throughput drug combination screens to identify single or 2-drug combinations to overcome resistance.
The role will involve the analysis of experimental data generated through the use of the functional genetic screens described above in both cancer cell lines and organoid models in order to define candidate drug resistance mechanisms and to understand the molecular pathways leading to resistance and the ways they may be overcome using drug combinations.
You will be working within a dynamic environment as part of a multi-disciplinary team formed of postdocs, students, bioinformaticians, statisticians and computer biologists. The team has unique experience performing high-throughput drug sensitivity screens and integrating these results with large-scale genomic datasets, together with mechanistic studies, to identify new therapeutic strategies and transition these finding into clinical trials. Candidates will have access to state-of-art facilities and resources including a high-performance compute cluster, large-scale functional screening infrastructure (chemical, RNAi, CRISPR, transposon), DNA sequencing pipelines and informatics support.
PhD or MSc (or equivalent) in Bioinformatics, Computer Science or Computational Biology or related discipline
Self-motivation and diligence
Organisational skills and accuracy
Good publication record or proven track record through work in industry
Good communication skills
Strong statistical background and analytical skills
Strong programming skills
Experience in computational genomics
Proficient in R or Matlab statistical packages
Background in cancer genomics
All cancers arise due to alterations in their genomes. Although insight into the genetic lesions in tumours by genome sequencing does already assist in selecting some drug regimens, it rarely results in disease eradication due to the emergence of drug-resistant clones. More sophisticated combination therapies in which several oncogenic pathways are targeted simultaneously or in a particular sequence are believed to hold more promise. However, at present we are unable to extract and interpret the necessary information from tumours to predict which drug regimen will be most effective.
It is the ambition of the team formed by members from Wellcome Trust Sanger Institute (WTSI) and the Netherlands Cancer Institute (NKI) to unravel the genomic and phenotypic complexity of human cancers in order to identify optimal drug combinations for personalized cancer therapy. Our integrated approach will entail (i) deep sequencing of human tumours and cognate mouse tumours; (ii) drug screens in a 1000+ fully characterized tumour cell line panel; (iii) high-throughput in vitro and in vivo drug resistance and enhancement genetic screens; (iv) computational analysis of the acquired data, leading to significant response predictions; (v) rigorous validation of these predictions in genetically engineered mouse models and patient-derived xenografts. This integrated effort is expected to yield a number of combination therapies and companion-diagnostics biomarkers that will be further explored in our existing clinical trial networks.
The Postdoctoral Fellow should typically be in his/her second postdoctoral position as part of their research training. The post is a three year fixed-term contract. We anticipate that the project will provide the applicant with a unique opportunity to develop analytical approaches to large-scale functional genetic screens in cancer models using state-of-the-art technologies.
The Genome Campus where the Institute is based offers excellent facilities including a start of the art data centre, gym, two cafes, a nursery, dining facilities, a cycle to work scheme, car sharing and free campus buses from various locations around Cambridge.
Equally important to campus life is the social activities offered by the Sports and Social Club whether it is a 'Burns night supper', the Christmas Ball or a quiz night there are opportunities to meet with people working across the organisation.
Our Benefits include: Defined Benefit Pension Scheme, Group Income Protection, Healthcare scheme, Childcare Vouchers, Nursery and Annual Leave 25 days plus Bank Holidays.
Closing date: 30th January 2015