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Exploring early pathogenic mechanisms driven by mutant ARPP21 ALS

Start Date:  1st October 2019

Award: 1 fully funded PhD studentship by KMRT JRC Application 2019

Project

Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease- MND) causes progressive muscular paralysis and death due to the degeneration of motor neurons in the brain and spinal cord. Cytoplasmic aggregates of the predominantly nuclear protein TDP-43 is the hallmark motor neuron pathology in 95% of cases. We recently identified 44 novel missense mutations in the RNA binding protein ARPP21 in 76 individuals from familial and sporadic amyotrophic lateral sclerosis (ALS) cases (under review at Nature Neuroscience).

Mutations in several other RNA binding proteins have been linked to ALS (MATRN3, TIA1, hnRNPA1/B2A1) but they are ubiquitous and multifunctional proteins whereas ARPP21 is expressed almost exclusively in neurons and is localized to the cytoplasm.

We will investigate ARPP21 on the earliest mechanisms driving cytoplasmic TDP-43 accumulation that disrupts RNA processing and initiates neurodegeneration. These mechanisms may define a novel common pathway for TDP-43 proteinopathy, the exploration of which could offer new targets for therapeutic intervention.

The student will acquire cutting-edge cell culture and molecular biology techniques and use start-of-the-art microscopy equipment in the Nikon Imaging Centre. The project will join one of the world’s leading ALS and FTD research laboratories, based in the newly built Maurice Wohl Clinical Neuroscience Institute. 

 Supervisors: 

Dr Younbok Lee and Professor Christopher Shaw

Institute of Psychiatry, Psychology and Neuroscience, De Crespigny Park, London SE5 8AF

 

Entry requirements: 


Standard PhD entry requirements: Applicants should have a Bachelors degree with 2:1 honours (or Overseas equivalent). A 2:2 degree may be considered only where applicants also offer a Masters with Merit.

 

Award types and eligibility:

Award cover Tuition fees, stipend.

Home and EU students only.

 

Further Informaiton: 

About the IoPPN (link to http://www.kcl.ac.uk/ioppn/about/index.aspx)

Studying at the IoPPN (link to http://www.kcl.ac.uk/ioppn/study/index.aspx)

MSc programmes at the IoPPN (link to http://www.kcl.ac.uk/prospectus/school/institute-of-psychiatry-psychology-and-neuroscience/programmes#graduate)

Research degrees at the IoPPN (link to http://www.kcl.ac.uk/ioppn/study/prospective-students/programmes-of-study/pgr/welcome.aspx)

KCL Researcher Development Programme (link to http://www.kcl.ac.uk/study/pg/school/RDP/training-and-development/Researcher-Development-Programme-2014-15.pdf) 

 

How to apply: 

Applicants must complete and submit an online admissions application, via the admissions portal by midnight (23:59 GMT), Sunday 28th April 2019. 

On the ‘Choosing a programme’ page, please select ‘Research degrees’ and enter the keyword Clinical Neuroscience Research MPhil/PhD (Full-time).

In your application, you will be asked to include:

  • Academic Transcripts – where applicable, academic transcripts must be submitted with the online admissions application
  • Details of your qualifications (you will need to attach copies)
  • Details of previous employment
  • A personal statement describing your interests and why you wish to apply for this project. Please include this as an attachment rather than using the text box.
  • Academic References – all admissions applications require two supporting references. If the applicant is relying on his/her referees to submit references directly to the College after he/she has submitted his/her admissions application, then the applicant must ensure that their chosen referees are made aware of the funding deadline.

 

In the Funding section, please tick box 5 and include the following reference: CAV-KMRT-2019

 

Please note there is no need to complete the Research Proposal section in your application as the project has already been set.

You are welcome to email younbok.lee@kcl.ac.uk (supervisor) for more information regarding the project and studentship.

 

If you have any queries regarding the application process, please contact Olivia Rees, Postgraduate Research Administrative Assistan

 

Closing Date: 28th April 2019 (23:59 GMT)

Interviews: 13th adn 14th May 2019

 

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