Postdoctoral Training Fellow - Ultanir Lab
Reporting to: Sila Ultanir, Group Leader
Contact term: This is a full-time, fixed term (4-year) position on Crick terms and conditions of employment.
Closing date and time: 30. 09. 2023 at 23:59
The Research Group
An exciting opportunity for a motivated postdoctoral scientist to join Kinases and Brain Development laboratory https://www.crick.ac.uk/research/labs/sila-ultanir at the Francis Crick Institute, London, UK. The postdoctoral position will be in collaboration with Dr Florencia Iacaruso laboratory, https://www.crick.ac.uk/research/labs/flor-iacaruso who uses state-of-the-art in vivo brain recordings and optogenetics methods in awake-behaving mice to analyse visual function (Iacaruso et al, 2017).
Dr Ultanir’s laboratory focuses on the role of protein kinases in neuronal development and function. Kinases regulate numerous cellular processes by phosphorylating their substrates and altering their function. CDKL5 is a brain enriched serine/threonine kinase. Loss of function mutations of CDKL5 cause a severe neurodevelopmental disorder with early-onset seizures, termed CDKL5 deficiency disorder (CDD). Our lab’s aim is to understand the roles of CDKL5 in the brain and to reveal how loss of CDKL5 leads to neuronal pathology.
Ultanir lab uses chemical genetics and mass spectrometry methods to determine the substrates and signaling pathways regulated by kinases in mouse models and human iPSCs. Other methods used in the lab include kinase biochemistry, transcriptomics, proteomics, slice electrophysiology, cellular live imaging assays and mouse behaviour. Our lab revealed CDKL5’s downstream effectors of microtubule binding proteins (Baltussen et al, 2018) and voltage-gated calcium channel Cav2.3 (Sampedro-Castañeda et al, 2022). Our discoveries led to a better understanding of CDKL5 function and pathology earning a Lab of the Year award from Loulou foundation of CDKL5 research. CDKL5 also functions in the nucleus and appears to be a critical regulator of neuronal differentiation yet its role in gene regulation is not well-understood.
How does CDKL5 regulates gene expression and circuit connectivity? Cerebral visual impairment is considered to be a major feature of CDD. CDD mouse models exhibit profound reductions in cortical visual evoked responses, visual acuity and contrast sensitivity. It is unknown how CDKL5 regulates the development of the visual circuitry in mice. The project aims to reveal substrates of CDKL5 and their function in building synaptic connections in visual circuitry. In this collaborative project, the postdoctoral fellow will use transgenic mouse models such as CDKL5 knockout mice, phosphomutant mouse models of CDKL5 substrates and other genetic interventions to determine critical signalling pathways for visual cortex development.
Postdoctoral Training Fellow will lead their own projects, are expected to contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and help train PhD students.
References
Iacaruso F, Gasler IT, Hofer SB (2017) Synaptic organization of visual space in primary visual cortex. Nature 547
Baltussen LL, Negraes PD, Silvestre M, Claxton S, Moeskops M, Christodoulou E, Flynn HR, Snijders AP, Muotri AR, Ultanir SK (2018) Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics. The EMBO journal 37
Sampedro-Castañeda M, Baltussen LL, Lopes AT, Qiu Y, Sirvio L, Mihaylov SR, Claxton S, Richardson JC, Lignani G, Ultanir SK (2022) Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability. bioRxiv: 2022.2011.2024.517538
Key experience and competencies
The post holder should embody and demonstrate our core Crick values:
Bold; Open; Collegial
Essential
PhD in neuroscience, biology or a related discipline or in the final stages of PhD submissionExperience in data analysis using, MATLAB, R or Python Good knowledge and experience in craniotomyTrack record of writing papers as evidenced by publications or submitted manuscripts in referred journalsEvidence of data presentation at scientific meetings
Desirable
In vivo brain recordings or imaging techniques in rodents Intracerebroventricular injections
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 [date] at 23:59All 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
