The genetic basis of cognitive impairment in intellectual disability and schizophrenia

Project description

Schizophrenia is a chronic mental health condition affecting 1% of human populations, with symptoms that include visual and auditory hallucinations, delusions and disordered thought, leading to disruption of the sense of self. Intellectual disability (ID) is an early-onset neurodevelopmental disorder that impacts on practical well-being and social skills and affects up to 3% of people. There is significant overlap between these common disorders, with families and individuals affected by both and with mechanistic overlap of the environmental and genetic factors involved. Much has been done to identify the underlying genetic causes, but it is evident that the known genes account for only a proportion of susceptibility and much remains to be discovered.

Working with local and international clinical colleagues, we have recruited a series of patients and families affected by either or both of these conditions, and are carrying out research to determine the underlying causes (eg Al-Amri A et al 2016, Am J Med Genet 170:1826-31; Klaus K et al 2017, Brain Behav 7:e00695). Current projects include studying a UK family with a Mendelian form of schizophrenia, whole exome sequencing in schizophrenia patients from Qatar where high consanguinity will increase the power to detect recessive susceptibility loci, and examining animal knockout models for a gene in which we found a mutation in a family with intellectual disability.

The student working on this project will use next-generation sequencing and bioinformatics to screen new families/cases with schizophrenia/ID for novel causative variants, then a variety of other techniques to determine the mechanisms involved. These could include generating and imaging cellular models by CRISPR gene editing; examining behaviour and pathology of relevant animal models; determining the normal expression pattern of the genes involved and the transcriptomic consequences of variants implicated; carrying out in silico modelling of the effects of specific mutations on the proteins involved; and other analyses as appropriate for the gene, variant and protein involved.

This project is in collaboration with Dr Steve Clapcote in the faculty of Biological Sciences. The appointed student will have the opportunity to learn and carry out bioinformatics analyses of next-generation sequencing, and to study the expression patterns and function of newly implicated genes and proteins using a wide range of molecular and cellular biology techniques. Depending on initial genomic findings, work may progress to genome editing and tissue culture, confocal microscopy, live cell imaging, transcript analysis, genome editing and protein modelling studies. This project has the potential to shed new light on human brain development, which is of immense interest both to scientists and to clinicians.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.

How to apply

Applications can be made at any time. Potential applicants should initially contact the lead supervisor Professor Chris Inglehearn with informal enquiries about this research project.

To formally apply for this project applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email.

If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email to inform us you would like to be considered for this scholarship project.