Elucidating the role of Calcyclin in the pathogenesis of ALS
To start: 1st October 2017
Award
1 fully funded IoPPN/MNDA PhD studentship
Project
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder. The underlying genetic architecture of the disorder is broad and exome sequencing of familial ALS samples (found in approximately 10% of total cases) has successfully identified six new ALS genes over the last five years eg. TUBA4a, TBK1, CCNF, CHCHD10, MATR3 and NEK1. Our group has recently identified another novel ALS gene, ANXA11 (recently published in Sci Transl Med. 2017 May 3;9 388). Annexin A11 (encoded by ANXA11) is a phospholipid and calcium binding protein, in which ALS mutations form insoluble aggregates in-vitro and in post-mortem tissue that also abolish binding to calcyclin.
The aim of this studentship is to unravel the role of calcyclin in Annexin A11 mediated ALS by studying specific Annexin A11 mutations in-vitro and in-vivo to determine disease mechanisms. A secondary goal is to determine the broader role of calcyclin in ALS pathogenesis.
The student will investigate the interaction of Annexin A11 and Calcyclin and conduct structural analysis using Biophysical Structural Binding Experiments with WT and Annexin A11 mutants e.g. Circular Dichroism (CD). Further investigation will be conducted in-vitro using cell lines, primary mouse cell lines, iPSCs and will characterize sub-cellular localization of Annexin A11/mutants and calcyclin, conduct apoptosis and calcium assays, and address the relationship of Annexin A11 with TDP43 pathology. Finally, the student will make a Calcyclin zebrafish model and work with an already established Annexin A11 zebrafish line to explore disease mechanisms.
The student will acquire cutting-edge biochemistry, cell culture and molecular biology techniques and use start-of-the-art microscopy equipment and actively interrogate ALS genes using Zebrafish models. The project is based primarily at the Maurice Wohl Clinical Neuroscience Institute, one of the worlds leading ALS and FTD research laboratories at Denmark Hill. The zebrafish component will be based within the laboratory of Professor Corinne Houart within the Department of Developmental Neurobiology at London Bridge.
Supervisors
Dr Bradley Smith, Dr Salvatore Adinolfi and Professor Corinne Houart.
Entry requirements
Applicants should have (or be expected to obtain) a 2:1 or 1st class honours degree in a subject relevant to the proposed project. If applicants already possess (or expect to obtain) a research-based MSc degree, a merit or distinction level is required.
Award type and eligibility
The studentships cover course fees (Home/EU rate); a stipend (approx. £17,000 per year) and a contribution towards research costs, training and conference attendance. See the MNDA website for terms and conditions.
How to apply
Applicants must complete and submit an online admissions application, via the admissions portal by midnight (12:00 GMT), Friday 9th June 2017.
On the ‘Choosing a programme’ page, please select ‘Research degrees’ and enter the keywords 'Clinical Neuroscience.'
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: BSMNDA2017.
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 Dr Bradley Smith (primary supervisor) for more information regarding the project and studentship.
If you have any queries regarding the application process, please contact the Postgraduate Research Administrator.
References must be received by the deadline for the applicant to be eligible.
Only shortlisted applicants will be contacted.
Further Information:
About the IoPPN
Studying at the IoPPN
MSc programmes at the IoPPN
Research degrees at the IoPPN
KCL Researcher Development Programme
Further information about the Motor Neurone Disease Association
Closing Date: Friday 9th June.
Interviews: 29th June 2017.