Associate Director/Principal Scientist Computational Biology

Associate Director/Principal Scientist Computational Biology

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Job Description: Associate Director/Principal Scientist Computational Biology

Company Description
NeoPhore is a biotech company targeting the dynamics of cancer neoantigen evolution through inhibition of the DNA mismatch repair ("MMR") pathway, by changing the genotype of the tumour, to discover effective, well-tolerated medicines that will provide the next generation of cancer immunotherapies. NeoPhore collaborates closely with many academic and commercial organisations, including NeoPhore's scientific founders Professor Alberto Bardelli and Dr Giovanni Germano at the University of Turin and Milan. NeoPhore currently has 13 full time employees and operates a mainly virtual drug discovery & development model. We have a dedicated internal Cancer Cell Biology (CCB) laboratory based at City St George's University, in South London, where most of the innovative Biology associated with the progression of a first-in-class molecule is being performed. An opportunity has arisen for a genomics next generation sequencing ("NGS") expert and talented Computational Biologist to join our team.

Role Description Summary
NeoPhore is seeking an experienced, independent, highly motivated, rigorous, and resilient computational biologist to lead our computational biology and bioinformatics function. A background in (immuno-)oncology is essential along with a strong desire to contribute to the progression of the understanding of a novel drug discovery field, through outstanding expertise in Bioinformatics & Genomics. Evidence for a flexible and cooperative approach to working in a dynamic, collaborative and multi-disciplinary team environment, together with strong team ethic, are also essential. The successful candidate will be leading the bioinformatics effort at NeoPhore, able to extract biological insights from experimental data, following a vast experience of contributing and/or overseeing the exploitation of computational pipelines for NGS data in genomics with tumour mutational burden and COSMIC mutational signatures.

Important aspects of this role include the ability to work and communicate effectively with team members and internal stakeholders from a wide variety of backgrounds. The ideal candidate will possess a strong desire to work in a fast-moving small molecule-focused translational research environment and needs to be highly self-motivated and organised. The position is remote with regular visits to the team in NeoPhore's CCB laboratory in London (UK).

Objectives and Responsibilities of this Role
NeoPhore's lead in Computational Biology & Bioinformatics will be a Genomics expert, responsible for executing the strategy and the data output from experimentally impactful cancer cell biology. Responsibilities include:

1. Lead on NeoPhore's Bioinformatics and Computational Biology strategy
2. Translation of long-term strategy into near-term tactical priorities for the computational biology and bioinformatics setup
3. Responsible for all the bioinformatics pipelines, internally and with CROs, AWS, data archiving, data presentation/interpretation and ultimate relevance in the context of immune-oncology clinical landscapes
4. Supporting NeoPhore's preclinical Genomics NGS analysis in collaboration with partner CROs
5. Development & optimisation of biomarker(s) of efficacy discovery and validation - genotypic changes characteristic of MMR inhibition
6. Selecting appropriate cellular models in vitro and in vivo preclinically
7. Identification of patient stratification biomarkers
8. Unravelling MMR-Biology and compound/MMRi MoAs
9. Contribute to clinical disease positioning
10. Assess and summarise literature findings to identify technical solutions and support project progression
11. Work collaboratively within a matrix environment
12. Analyse and interpret experimental results using data analysis software tools, including in the context of online databases and platforms
13. Communicate and present scientific data in a timely fashion to contribute maximum impact to project strategy and decision-making
14. Maintain an up-to-date Bioinformatics storage compatible with due diligence
15. Drive innovation in computational biology methods and stay abreast of the latest developments in the field

The data produced is expected to make a significant impact on NeoPhore's understanding of the MMR pathway and the discovery of small molecule therapeutics.

Previous experience required for this Role

1. Minimum of 7 years of industry experience in Computational Biology or Bioinformatics with experience building and/or leading computational biology and/or bioinformatics in the biotech or pharmaceutical drug discovery sectors preferred but relevant experiences within the academic setting will also be considered.
2. Expertise preclinically in murine cell models will be highly advantageous.
3. Expertise in preclinical human cancer cell models is required, cell lines, CDXs, PDXs and ideally clinical samples with both solid and liquid biopsies.
4. Previous experience in a clinical stage company will be considered advantageous.
5. Successful exemplification of high-quality scientific achievement through computational pipelines to enable the generation of biological insights, specifically with NGS.
6. Previous involvement in biomarker discovery and implementation.
7. Demonstrated ability to work collaboratively in a multidisciplinary setting.
8. Good knowledge of small molecule translational research.
9. Knowledge of DDR in immuno-oncology will be advantageous and/or Colorectal cancer and/or MSI vs. MSS tumours (preferable).

Qualifications
PhD in biological sciences; Computational Biology, Bioinformatics, Computer Science, Statistics, or a related field - ideally, in (immuno-)Oncology.

Skills Required:

1. NGS analysis expert - particularly WES at high depth, but also low pass WGS: TMB (including a qualitative assessment; SNVs, Insertions, Deletions); COSMIC mutational signatures (SBS, DBS, ID) including robust deconvolution and Cosine similarity scores; Mutational gains and enrichment with COSMIC signatures relationship.
2. MSI status (MSI scores from NGS; other technologies including databases predictions).
3. Neoantigen and MHC binding prediction knowledge and experience - insights into genomics & immuno-oncology relationships, particularly with regards to adaptive immune responses.
4. Knowledge of the interrogation of relevant oncology online databases.
5. Storage of raw data, pre-analysed data and fully analysed data with presentation skills to internal organisation as well as external stakeholders. Due diligence experience will be advantageous.
6. Evidence for excellent, concise oral and written communication skills; for example oral presentation of key findings, on a Teams call with various members of the team - this is critical in the context of a virtual operational mode.
7. Attention to detail, highly organised, with evidence for successful time-management and an ability to work under pressure towards tight deadlines.
8. Active listening skills that enable effective implementation of plans agreed with senior management and in team discussions.
9. Team player at heart with excellent inter-personal skills for building and maintaining good working relationships both within the NeoPhore team and with partner CROs and collaborators.

Preferred:

1. Previous experience working with external CROs.
2. Extensive knowledge of DepMap from the Broad Institute.
3. Insights into MMRd/MSI-H genotypic features (COSMIC) in oncology and hereditary diseases CMMRD and Lynch - capacity to interrogate related and relevant databases and/or insights into the specifics of colorectal cancer and/or insights into microsatellite analysis, including MMRpredict score.
4. Insights into the clinical context of checkpoint blockade in immuno-oncology.
5. Insights into Werner and therapeutic intervention context/programs - DNA secondary structures during/post-replication.
6. RNAseq, Nanostring, pathway analysis insight and capabilities (including in the context of Immuno-Oncology).
7. Epidemiology analysis in the context of cancer (genotoxic inducers).

Appointment Details:
The full-time position is home-based with regular visits to the CCB laboratory facilities, based at City St George's University, London, UK, and reporting to the Director of Biology. Compensation package to be agreed according to qualifications, including competitive salary, as well as benefits.