The Francis Crick Institute is a partnership between Cancer Research UK, the Medical Research Council, the Wellcome Trust, UCL (University College London), 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. Due to open in 2015, the Crick will be located in a new, purpose built research centre in Brill Place, St. Pancras and will house some 1,500 staff.

Objectives: The Postdoctoral Training Fellow will use innovative mouse genetics to understand the pathological mechanisms underlying Down Syndrome (DS). In particular the postdoc will engineer novel mouse models containing human chromosome 21 (Hsa21) in which the human chromosome can be inducibly silenced in specific cell types, or at defined times in development or adult life.

Specific objectives will include, but not be limited to:

• Evaluate several human ES and iPS cell lines as suitable donors of Hsa21 using CGH and exome sequencing.
• Build an inducible XIST construct and target this into Hsa21.
• Transfer targeted Hsa21 into mouse ES cells.
• Generate chimeric mice from ES cells carrying targeted Hsa21 and breed to transmit the extra chromosome through the germline, establishing the Tc2 mouse strain.
• Cross Tc2 mice to inducible and/or tissue-specific Cre drivers to inactivate Hsa21 in tissue of choice or at time of choice.
• Use this system to study which tissues need to have Hsa21 in them to cause DS-like phenotypes, and whether inactivation of Hsa21 in adult life results in reversal of DS phenotypes.

Such an inducible model will allow determination if the phenotypic effects of an extra copy of Hsa21 can be reversed by silencing the chromosome in adult life, or whether the phenotypes are all set during embryonic development. Similarly the inducible model will allow studies of the cell types in which an extra copy of Hsa21 is required to result in DS phenotypes.

Person Specification

Essential

• PhD in molecular biology, developmental biology or neuroscience
• Experience in molecular biology and cell biology techniques
• High degree of independence, motivation and creativity to solve difficult technical challenges.

Desirable

• Experience in mouse genetics
• Experience and knowledge in developmental biology, especially of the heart or the nervous system.

For the full job description: http://crick.ac.uk/media/222647/277._postdoctoral_training_fellow_-_genetics_in_down_syndrome.pdf

If you would like to apply for this role, please submit your CV and a covering letter, explaining your motivation and suitability for this role and stating your current salary, to Victor.T@crick.ac.uk with ‘Postdoctoral Training Fellow – Genetics of Down Syndrome – REF 277’ in the subject line.

The closing date for applications is 12 May 2015 at 5pm.

Should you have any queries relating to this role, please contact Victor Tybulewicz Victor.T@crick.ac.uk , or Nicola Texeira, Resourcing Advisor via jobs@crick.ac.uk.