Functional analysis of Gorlin Syndrome links to genome stability maintenance and S-phase checkpoints regulation in response to DNA damage

Gorlin Syndrome (GS) is an autosomal dominant disorder that is characterized by multiple systemic and musculoskeletal developmental abnormalities (Gorlin and Goltz, N Engl J Med 262: 908,1962) as well as predisposition to cancer. GS patients develop multiple basal cell carcinomas (BCC) as well as extracutaneous tumours such as medulloblastomas, meningiomas, fibromas and rhabdomyosarcomas (Athar et al; Exp Dermatol 15: 667, 2006). The syndrome results from germline mutations of the human homologue (PTCH) of Drosophila segment polarity gene patched (ptc) (Hahn et al; Cell 85:841, 1996, Johnson et al; Science 272:1668, 1996). The PTCH1 gene is the main negative regulatory component of Hh signalling. In the absence of PTCH1 the pathway is constantly upregulated. The hedgehog (Hh) signalling pathway is one of the most fundamental signal transduction pathways in embryonic development in vertebrae that also regulates many adult homeostatic processes including stem cells renewal and differentiation. While the connection between aberrant Hh signalling in transcription regulation resulting in developmental defects is being intensely studied, the underlying mechanisms affecting genome stability maintenance leading to tumour formation are not well understood. Our pilot data using PTCH1 mouse knock-down system strongly indicate that constitutively active Hh signalling disrupts DNA replication surveillance mechanisms and DNA double-strand break repair in response to DNA damage. The molecular mechanisms underlying these defects will be investigated in this research project. 

PhD programmes are for those who are seeking to develop greater in-depth knowledge in a specific area. Completing this level of study is about making an original contribution to knowledge, making new discoveries and developing lifelong skills. 

At Aston University, our Engineering and Physical Sciences PhD programmes will provide all the support and facilities you will need to develop into a leading researcher in your chosen field.  You will be welcomed into a supportive community with a shared enthusiasm for original research, where diversity and multidisciplinary is championed.

For formal enquiries about this project contact:

Dr Boris Kysela
Dr Theo Kantidakis

Candidates should have been awarded, or expect to achieve, EITHER:
•    A Bachelors degree in a relevant subject with an award of First Class or 2.1. 
OR 
•    A Bachelors degree in a relevant subject with an award of First Class or 2.1, and a Masters degree in a relevant subject with an award of Merit or higher.
Qualifications from other countries which are considered by Aston University to be equivalent to that described above will be eligible to apply.

Essential criteria:
•    Good Coding Skill and willing to evolve them along the journey. 
•    Basics on IP networking
 

We can only consider applications that are complete and have all supporting documents. Applications that do not provide all the relevant documents will be automatically rejected. Your application must include: 

1. English language copies of the transcripts and certificates for all your higher education degrees, including any Bachelor degrees.
    
2. A Research Statement detailing your understanding of the research area, how you would approach the project, and a brief review of relevant literature. Be sure to use the title of the research project you are applying for. There is no set format or word count. 
    
3. A personal statement which outlines any further information which you think is relevant to your application, such as your personal suitability for research, career aspirations, possible future research interests, and further description of relevant employment experience. 
    
4. Two academic referees who can discuss your suitability for independent research. References must be on headed paper, signed and dated no more than 2 years old. At least one reference should be from your most recent University. You can submit your references at a later date if necessary. 
    
5. Evidence that you meet the English Language requirements. If you do not currently meet the language requirements, you can submit this at a later stage. 
    
6. A copy of your passport. Where relevant, include evidence of settled or pre-settled status.

Interviews

Interviews will be conducted online via Microsoft Teams. If you are shortlisted, you will be contacted directly with details of the interview.  

Contact information

For formal enquiries about this project, contact Dr David Benton

Studying a PhD is great route into academia and industries that are centred on research and innovation. Areas with a demand for very high level and specialised research skills often demand PhDs.

In addition to this specialist knowledge, PhD education will help you to develop a set of valuable transferrable skills. The very nature of studying an intensive research degree will enable you to become a team player, develop problem-solving skills, analytical thinking, and advanced presentation and communication skills.

The variety of PhD project topics at Aston means that the destinations of our graduates vary substantially. Some choose to continue into academia, at either Aston or other leading institutions, while others go onto use their newly acquired skills in a range of research, healthcare, industry or charitable fields. When selecting your chosen PhD path at Aston, your supervisor will be able to provide you with relevant career opportunities that could be available to you in your specialist area.