The influence of JAKMIP1, a key risk gene for autism, on neural circuit function. PhD in Medical Studies (MRC GW4 BioMed DTP) Ref: 3648
About the award
Dr Asami Oguro-Ando, The Institute of Biomedical and Clinical Science, College of Medicine and Health, University of Exeter
Dr Paul Chadderton, School of Physiology, Pharmacology & Neuroscience, University of Bristol
Prof Jonathan Mill, College of Medicine and Health, University of Exeter
This studentship aims to understand the influence of JAKMIP1 dysfunction on neural circuit activity in the cerebellar and cerebral cortices. Autism is a major mental health issue affecting 1 in 100 people in the UK, defined by three core features, primarily impaired social interactions, language impairment, and repetitive or restricted behaviours. Along with the cerebral cortex, the cerebellum, or ‘little brain’, is increasingly implicated in the expression of autism-like behaviours. Autism has a strong genetic component, but the mechanistic links between behavioural phenotypes and molecular- and brain circuit pathology are poorly understood. Recently, dysfunction of janus kinase and microtubule interacting protein 1 (JAKMIP1), a regulator of neuronal translation and glutamatergic signalling, has been shown to contribute to both inherited and idiopathic autism. The JAKMIP1 protein is involved in core autism behaviours including social defects (Berg et al., Neuron 2015). To understand the molecular functions of JAKMIP1, we have knocked out JAKMIP1 in human neuroblastoma cells using the novel genome-editing technique, CRISPR-Cas9 system. We will identify the specific cellular cascades targeted by JAKMIP1 and investigate their links with autism. We will then explore how JAKMIP1 deficiency induces social dysfunction and motor coordination through altered neural circuit activity in the brains of JAKMIP1-KO mice.
Experimental Design: This project will combine novel cutting-edge techniques including bioinformatics, genome-editing, molecular cellular biology, microscopy and in vivo electrophysiology to address the following specific aims: 1. Identify potential therapeutic targets for modifying autism-associated neuronal and brain morphological phenotypes by:
a. RNA-sequence data analysis (bioinformatics and Crispr genome engineering): Identify cellular pathway candidates for pharmacological modulation using JAKMIP1-KO neuroblastoma cells.
b. Molecular biological analysis (neuronal morphological analysis and target pathway analysis in vitro): Detect target pathways of JAKMIP1 by examining protein/mRNA levels using western blot and qPCR.
c. Brain anatomical screening (Immunohistochemistry and confocal microscopy): Measure the effect of Jakmip1 loss on development in the cerebellum and cerebral cortex.
2. Characterise how JAKMIP1-deficiency alters information processing in neural circuits by:
a. In vivo electrophysiological recording in Jakmip1-KO mice: Measure neuronal ensemble activity with NeuroPixels probes in the cerebellum and cerebral cortex of awake behaving animals.
b. Functional neuronal connectivity in JAKMIP1 dysregulated brain: Assay strength and dynamics of synaptic connections using optogenetics in Jakmip1-KO mice.
The successful candidate will establish the influence of a key autism risk gene on neural processing, potentially leading to new breakthroughs in diagnosis and intervention.
This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£15,009 for 2019/20, updated each year) for 3.5 years.
For further information relating to the funding please see the main MRC GW4 BioMed website
This project is in competition with a number of other projects across the partnership; up to 18 studentships in total will be available.
Eligibility and Residency Requirements
To be eligible for a full award (fees and stipend) from a Research Council, a UK or EU student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship.
An EU student who has not been resident in the UK for at least 3 years prior to the start of the studentship is generally eligible for a fees-only award from the Research Council: to be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU; in the same way as UK students must be ordinarily resident in the UK.
For our regular recruiting round, the Doctoral Training Partnership has additional funding from the partner universities to support a limited number of EU students who do not meet the UK residency requirements, so long as they meet the criteria for a fees-only award: these studentship will therefore be fully funded (fees and stipend).
For full details on eligibility, please refer to the MRC GW4 BioMed website
Students with 'International' status are unfortunately not eligible to apply.
If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.
Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).
For further information regarding data protection for the Application Process and if you become a student on one of the Programmes please click here
For an overview of the MRC GW4 BioMed progamme, please see the website www.gw4biomed.ac.uk
In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences, and can fund additional training, including Masters to assist discipline conversion. Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.
If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.
How to apply
Applications Open on 29 September and close at 17:00 on Monday 25 November 2019
You will need to complete an application to the GW4 BioMed MRC DTP for an 'offer of funding'
Applying for an 'offer of funding'
Please complete the application form at https://www.gw4biomed.ac.uk/doctoral-students/ by 5pm Monday 25 November 2019.
The Research Theme Panels will complete the shortlisting and will aim to inform applicants by Thursday, 19 December 2019. If you are shortlisted you will need to:
- contact the lead supervisor of you chosen project in which you are interested, to arrange an informal interview (which can be in person, by telephone or by Skype) between 3 and 15 January 2020. Please note that interview expenses will not be available for candidates to attend these meetings.
- attend a formal interview, with a panel of four academics which will take place in Cardiff on 21 and 22 January 2020.
For further details of the application process please see the following web page www.gw4biomed.ac.uk/doctoral-students/
You do NOT need to apply to the University of Exeter at this stage - only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.
|Application deadline:||25th November 2019|
|Value:||Stipend matching UK Research Council National Minimum (£15,009 p.a. for 2019/20, updated each year) plus UK/EU tuition fees|
|Duration of award:||per year|
|Contact: PGR Recruitmentfirstname.lastname@example.org|