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Postdoctoral Project Research Scientist - Signalling and Structural Biology Laboratory

Employer
Francis Crick Institute
Location
London (Central), London (Greater) (GB)
Salary
From £43,210 with benefits, subject to skills and experience
Closing date
1 Aug 2024

View more

Discipline
Life Science
Job Type
Researcher
Employment - Hours
Full time
Duration
Fixed term
Qualification
PhD
Sector
Academia

Job Details

Postdoctoral Project Research Scientist - Signalling and Structural Biology Laboratory

This is a full-time, fixed term (12 months initially, with a possible one-year extension) position on Crick terms and conditions of employment.

Project summary

The Francis Crick Institute is recruiting a lab-based postdoctoral project research scientist to lead on the development of agonist antibodies that promote neuro-regeneration in neurological disease. The successful candidate will join the laboratory of Dr N.Q. McDonald (https://www.crick.ac.uk/research/labs/neil-mcdonald) and will collaborate with both the Neurodegeneration Biology Laboratory (https://www.crick.ac.uk/research/labs/sonia-gandhi) and Dom Bonnet at the Francis Crick Institute. The position is fully funded by the idea-to-innovation programme at the Crick to translate basic research findings into therapeutics.

The Research Group

The Signalling and Structural Biology Laboratory studies kinase-driven control mechanisms, assemblies and networks, focusing on processes such as neuro-regeneration, 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 & https://www.varianbio.com). 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:  http://www.crick.ac.uk/research/labs/neil-mcdonald.

The Project background

The chronic degenerative disorder Parkinson’s disease (PD) affects both the motor and non-motor systems within the central nervous system. The motor symptoms of the disease result from the death of midbrain dopaminergic neurons within the substantia nigra. The cause of this cell death is poorly understood but involves protein aggregates within Lewy bodies present in these neurons. There is no known cure for PD, and treatment aims to mitigate symptoms. In the course of our discovery research programme, we identified agonist antibodies against the RET receptor tyrosine kinase, a known pro-survival signalling receptor for adult dopaminergic neurons. These antibodies present as new therapeutic modalities to elicit neuroprotective responses, extend neuronal survival and even reverse PD disease pathology. Following extensive characterisation of the agonist antibody, we are now seeking to develop it as a therapeutic, and thus demonstrate its potential for commercialisation. This post will be funded by an idea-to-innovation grant, which commits to supporting this work towards commercialisation, if milestones are met. It will enable the successful candidate to join an exciting antibody development project at an early stage.

Key responsibilities

These include but are not limited to:

  • To produce and characterise agonist antibodies and variants for use in dopaminergic neurons programmed from PD patient-derived iPSCs.

  • To assess the potency of the antibody on different neuronal cell lines.

  • Engage with collaborators to reformat the antibody and undertake a structure-guided antibody affinity maturation.

  • To pilot trans-well experiments to assess antibody properties at crossing the blood-brain-barrier using an in vitro model.

  • To act as the de facto project manager, liaising with collaborators and Crick service providers.

  • To present results at internal meetings, conferences and, ultimately, to funders and investors.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, imaginative, open, dynamic and collegial, in addition to the following:

Essential

  • PhD in Protein Biochemistry or in the final stages of PhD submission ideally with experience of antibody generation

  • A good understanding of in vitro display technologies e.g. phage and/or yeast display 

  • Experience in biochemical characterisation techniques; ELISA, flow cytometry, FACS, SPR and/or Bio-layer interferometry (BLi)

  • Motivated and driven, with excellent communication skills

  • Track record of writing papers as evidenced by publications or submitted manuscripts in peer reviewed journals

  • Willingness to learn new experimental skills

  • Self-motivated with the ability to work independently and to meet deadlines.

  • Good organisational skills and able to interact constructively within a multidisciplinary group

Desirable

  • Knowledge and experience in biochemistry, enzymology and/or structural biology

  • A strong interest in modern drug discovery methods

  • Experience in protein purification

  • Computing experience, in particular Linux-based environments

About Us

At 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 website.

  • The closing date for applications is 1st August, 2024 at 23:59

  • 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

Application Instructions

If you are interested in applying for this role, please reach out to neil.mcdonald@crick.ac.uk. 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 & 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: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/equality-diversity-and-inclusion

Find out what benefits the Crick has to offer:

For more information on our great pay and benefits package please click here: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/pay-and-benefits

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: https://www.crick.ac.uk/careers-and-study/life-at-the-crick/equality-diversity-and-inclusion

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