Postdoctoral Project Research Scientist – Signalling and Structural Biology Laboratory

Job title:

Postdoctoral Project Research Scientist – Signalling and Structural Biology Laboratory

Company

Francis Crick Institute

Job description

Salary for this Role:From £43,210 with benefits, subject to skills and experienceJob Title: Postdoctoral Project Research Scientist – Signalling and Structural Biology LaboratoryReports to: Neil McDonaldClosing Date: 17/Aug/2024 23.59 GMTJob Description:Postdoctoral Project Research Scientist – Signalling and Structural Biology LaboratoryThis is a full-time, fixed term (24 months) position on Crick terms and conditions of employment.The Research GroupWe seek a talented and highly motivated post-doctoral project research scientist to work on a Cancer Research Horizon funded project to discover chemical inhibitors targeting stromal protein kinase C beta in B cell malignancies. The project is based in Neil McDonald’s laboratory at the Francis Crick Institute in collaboration with the clinician-scientist Ingo Ringshausen (UCL Cancer Institute) with medicinal chemistry support from the Francis Crick Chemical Biology Science Technology Platform.The Signalling and Structural Biology Laboratory studies kinase-driven control mechanisms, assemblies and networks, focusing on processes such as neuroregeneration, cell polarity and cell fate. Our goal is to understand how kinase control mechanisms are subverted in different human diseases. In parallel we have developed biological and chemical tools against neurotrophic and polarity protein kinase targets. In some cases, these tools have led to the development of lead clinical candidates (PMID: 23418854 & ). Research techniques used in our multidisciplinary laboratory environment include cryo-electron microscopy, X-ray crystallography, cryo-electron tomography, biochemical and biophysical methods, chemical biology, cell culture models for neuronal differentiation and cell polarity. Details of research projects currently being undertaken can be seen at: .The ProjectThe project focusses on protein kinase C beta (PKC-ß) as a stromal target in haematological malignancies and solid cancers and is supported by an experienced drug discovery team including Peter Parker (Emeritus at the Crick Institute) and Verity Sabin (Discovery Chemistry, Cancer Research Horizons). PKC isoforms are known to play crucial roles in human cancer and PKC-ß specifically is linked to adult T-cell leukemia (ATL) and B cell malignancies (PMID:28627735 and 33177705). Recent evidence has demonstrated that stromal cell PKC-beta activity is required for disease progression in lymphoid cancers and chemical inhibition of stromal PKC-beta shows therapeutic benefit (PMID: 31941829). The project’s goal is to build a chemical data package around PKC-β inhibition using a structure-guided approach from published and unpublished crystal structures. Intermediate scaffolds are available for progression using biophysical methods and in cellulo screening. In parallel, an X-Chem approach to drug discovery will be pursued in collaboration with the DIAMOND Synchrotron Light Source. The post-holder will play a leading role in the delivery of this drug discovery project, from the purification and structure determination of PKC-beta-inhibitor complexes, the co-design of successive rounds of inhibitors with medicinal chemists, characterisation using biophysical methods and subsequent assay using biochemical and in vivo mouse cancer models. Training can be provided for the structural and chemical biology components of the project. The project would suit candidates interested in academic drug discovery or considering a transition from academia into industry.Key experience and competenciesThe post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:EssentialPhD in structural/enzymology/chemical biology or in the final stages of PhD submissionA good knowledge and experience in biochemistry, enzymology and/or structural biologyExperience in molecular biologyTrack record of writing papers as evidenced by publications or submitted manuscripts in peer reviewed journalsEffective written and verbal communication skillsEvidence of data presentation at scientific meetingsExperience of experimental designWillingness to learn new experimental skillsSelf-motivated with the ability to work independently and to meet deadlines.Good organisational skills and able to interact constructively within a multidisciplinary groupDesirableA strong interest in modern drug discovery methodsExperience in protein purificationExperience in biophysical methods of protein characterisationComputing experience, in particular Linux-based environmentsAbout UsAt the Crick, we conduct research at the forefront of biomedical research. We combine rigour with an open and collaborative culture, and are outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources.We have a wide research portfolio with no divisions or departments, bringing biomedical researchers together with clinicians, physical scientists and applied scientists from our pharmaceutical partners.We aim to attract the most talented researchers and support them to tackle innovative research questions. Our science technology platforms provide our researchers with access to state-of-the-art technology and expertise.We provide an excellent learning environment with dedicated education programmes in public engagement with science, education and personal development, and a postdoc training programme that prepares scientists for leadership roles in science.If you are interested in applying for this role, please apply via our .All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.If you require a visa to work in the UK we will help support your application should you be successfulApplication InstructionsIf you are interested in applying for this role, please reach out to neil.mcdonald@crick.ac.uk with a CV, cover letter, and information about your start date timeframe. All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom. If you require a visa to work in the UK we will help support your application should you be successful.Equality, Diversity & InclusionWe welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.Read more on our website:Find out what benefits the Crick has to offer:For more information on our great pay and benefits package please click here:Equality, Diversity & Inclusion:We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.Read more on our website:

Expected salary

Location

London

Job date

Sat, 20 Jul 2024 03:45:33 GMT

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