Number of awards:
Start date and duration:
September 2018 for 3 years.
We have unequivocally established that endoplasmic reticulum (ER) stress, induced in chondrocytes as a result of accumulated mutant protein, is the primary cause of growth plate dysplasia and reduced bone growth in a group of genetic skeletal diseases (GSDs). Moreover, we have demonstrated that reducing ER stress through the administration of carbamazepine (cbz), in both cell and mouse models, restores cell homeostasis and bone growth in metaphyseal chondrodysplasia type Schmid (MCDS). A multi-national clinical trial of cbz for therapeutic intervention in MCDS will start in January 2018 [MCDS-Therapy; EU Horizon2020].
A key underpinning activity of MCDS-Therapy is identification of novel biomarkers and correlation with clinical outcomes for future monitoring of treatment efficacy. We are collaborating with Sciomics (Heidelberg) who will use their scioDiscover platform (semi-targeted affinity proteomics) to identify biomarker candidates during the course of the project using a variety of cell, mouse and patient samples.
The specific aims of this PhD project are to identify novel snoRNAs and microRNAs as potential biomarkers for growth plate dysplasia in MCDS and measure their repsonse to cbz treament. Global miRNA expression profiles will be generated and analysed using the latest technology. Moreover, for this PhD project we will also have access to iPSC/MSC cell lines from MCDS patients enrolled in the study as well as mouse models to identify biomarker signatures (+/- cbz treatment). This study will allow comparison of novel miRNAs/snoRNAs with protein signatures (Sciomics) correlated to clinical response.
Mullan LA, et al. J Clin Invest. 2017 Oct 2;127(10):3861-3865.
Briggs MD, et al. Expert Opin Orphan Drugs. 2015 Oct 3;3(10):1137-1154.
Newcastle University, Faculty of Medical Sciences (https://bitly.im/WdXjN
Name of supervisor(s):
Professor Michael Briggs (https://bitly.im/bGqFL
) and Professor David Young, Institute of Genetic Medicine.
You must have, or expect to achieve, at least a 2:1 Honours degree in biomedicine, genetics, or a related area. A further qualification such as an MSc or MRes is advantageous.
This award is available to UK/EU applicants.
To study this course you need to meet the following English Language requirements:
IELTS 6.5 overall (with a minimum of 5.5 in all other sub-skills).
How to apply:
You must apply through the University’s online postgraduate application system (https://bitly.im/7vgzm
). To do this please ‘Create a new account’.
Only mandatory fields need to be completed. However, you will need to include the following information:
•insert the programme code 8300F in the programme of study section
•select ‘PhD in the Faculty of Medical Sciences – Institute of Genetic Medicine as the programme of study
•insert the studentship code GM001 in the studentship/partnership reference field
•attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code GM001 and state how your interests and experience relate to the project
•attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications.
* The online application system will only allow one application using the programme code 8300F. If you are applying for TWO or more projects using that code then you will need to email our Postgraduate Admissions Service ([email protected]
) with the following information:
•your application number (from the first project application that you submitted online)
•the second studentship code and its corresponding title
•a two page covering letter for the second project
Our Postgraduate Admissions Service will then forward this information to the relevant selector in the Faculty of Medical Sciences.