Postdoctoral Project Research Scientist

Postdoctoral Researcher - Ultanir Lab (Francis Crick Institute) & Isalan Lab (Imperial College London), In this project, we aim to develop ZFPs which can upregulate CDKL2 mRNA expression and test if these can rescue molecular, cellular and behavioural defects in CDKL5 deficiency models. Postdoctoral researcher will generate and test zinc finger protein transactivators. They will then use CDKL5 knockout mouse models to determine if they can restore CDKL5-mediated functions at molecular and behavioural level. iPSC derived neurons of CDD models will also be used to test rescue of phosphorylation substrates. Postdoctoral researcher will lead their own projects, contribute to other projects on a collaborative basis and help train PhD students.

• PhD in biology, biochemistry, neuroscience or a related discipline or in the final stages of PhD submission
• Good knowledge of molecular biology skills
• Track record of writing papers as evidenced by publications or submitted manuscripts in referred journals
• Evidence of data presentation at scientific meetings
Desirable
• Experience in research with iPSC derived neurons
• Experience in RNA sequencing
• Experience in mass spectrometry
• Experience in neonatal brain injections or in utero electroporations
• Experience in mouse behavioural analysis
  
  We are recruiting a motivated postdoctoral scientist to join the labs of Kinases and Brain Development https://www.crick.ac.uk/research/labs/sila-ultanir at the Francis Crick Institute, London, UK and Mark Isalan at Imperial College London https://profiles.imperial.ac.uk/m.isalan. The postdoctoral scientist will run a translational project to develop zinc finger protein transactivators for treatment of a neurodevelopmental disorder.
Ultanir's laboratory studies the roles of protein kinases in neuronal development and function. Kinases regulate numerous cellular processes by phosphorylating their substrates. A major focus in the lab is understanding the functions of a serine/ threonine kinase called CDKL5. CDKL5 is highly expressed in the brain. Loss of function mutations in CDKL5 cause a neurodevelopmental disorder with early-onset seizures and profound neurological defects, termed CDKL5 deficiency disorder (CDD). Patients with CDD require life-long care. There are no disease targeting therapies for CDD. We identified several phosphorylation substrates of CDKL5 in the developing brain and defined their roles (PMID 38081835, 30266824 & Lopes et al, BioRxiv, 2024). Using these phosphorylations as read-outs of CDKL5 activity, we demonstrated that CDKL2, a kinase similar to CDKL5, can phosphorylate common substrates with CDKL5 (PMID 38326557). CDKL5 is on the X chromosome leading to mosaic expression in patients. CDKL2 is broadly expressed in neurons. Increasing CDKL2 expression can therefore be a therapeutic avenue. The Isalan lab has long worked on a zinc finger engineering platform for gene therapy (PMID 11433278, 23054839, 27600816). Zinc finger proteins (ZFPs) can be engineered to make tools to control genes via viral vector delivery, especially using adeno-associated viruses (AAVs; 35223884). The ZFP modular platform drives robust activation or repression of target genes. Since many zinc fingers have human origins, they can be delivered long-term to patients without causing a strong immune response., 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., The Francis Crick Institute (the Crick) is a partnership between the Medical Research Council (MRC), Cancer Research UK (CRUK), the Wellcome Trust, University College London (UCL), Imperial College London and King's College London. It is a registered charity whose purpose is to conduct biomedical research into all aspects of human health and disease. The institute will be a world-leading centre of biomedical research and innovation. It will promote connections between researchers and disciplines and between academic institutions, healthcare organisations and businesses. Dedicated to research excellence, the institute will have the scale, vision and expertise to tackle the most challenging scientific questions underpinning health and disease. It will be world-class with a strong national role - training scientists and developing ideas for public good. On 1 April 2015, staff from the London Research Institute (CRUK) and National Institute for Medical Research (MRC) transferred to the Crick to form a fully functional research institute on four sites. In 2016, the Crick will move to a single new, purpose-built research centre in St. Pancras which will house some 1,500 staff.


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• If you require a visa to work in the UK we will help support your application should you be successful
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