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PhD studentship: The role of silent  DNA in cancer development

Studying the hypothesis that the loss of STAG2 in cancer leads to the mis-organisation of heterochromatin structure, mis-regulation of repetitive sequences therein,  and increased genome instability.

  • Primary supervisor: Dr Suzana Hadjur 
  • Secondary supervisor: Prof Simona Parrinello

APPLICATIONS CLOSED (Monday 11 January 2021 17:00 (GMT)


Project 

Repetitive DNA sequences comprise the vast majority of our genome, yet nearly all cancer genomics studies focus on expression of protein-coding genes. New evidence is beginning to show that the ‘re-awakening’ of silent parts of the genome plays an important yet poorly understood role in cancer development.  Pan-cancer studies have revealed that cohesin, and in particular its regulatory component STAG2, is commonly inactivated in cancer.  Why inactivating STAG2 mutations are selected in cancer is not well understood.   

 We have discovered that STAG proteins play a critical role in the formation of repressive heterochromatin structures which function to maintain silencing of repetitive elements.  The PhD student will study the hypothesis that the loss of STAG2 in cancer leads to the mis-organization of heterochromatin structure, mis-regulation of repetitive sequences therein,  and increased genome instability.  This represents a novel opportunity to understand the roles of STAG2 mutations in tumorigenesis.  This study will also contribute to the broader understanding of how changes to heterochromatin and repetitive element de-repression contribute to cancer development.    

The student will develop their skills in mammalian cell culture including CRISPR-mediated engineering of patient-derived cell lines; computational analysis of RNA-sequencing data of glioblastoma cell lines derived from patients; genomic methods for protein-chromatin analysis and confocal imaging and quantitative analysis using Imaris software tools.   

More detailed information about the research project is available on request from s.hadjur@ucl.ac.uk  

Person specification

Essential 

  • Minimum upper second class Honours Degree in an associated discipline, or an overseas qualification of an equivalent standard. 
  • Knowledge of mammalian cell culture, basic molecular biology protocols and statistics.  
  • Preliminary knowledge of research techniques. 
  • Evidence of motivation for and understanding of the proposed area of study. 
  • Ability to develop understanding of complex problems and apply in-depth knowledge to address them. 
  • Potential to develop expertise in new areas of the subject. 
  • Potential for innovation and initiative, and evidence of an ability to work independently. 
  • Effective communication skills in both written and spoken English. 

Desirable 

  • Relevant laboratory research experience. 
  • Experience of chromatin/epigenetic-based laboratory techniques, next-generation sequencing or analysis. 
  • Experience with running R scripts and computational skills.  

Students will also need to qualify as UK/EU fee payers and meet UCL general admissions criteria

 
Duties and responsibilities

Research 

  • To apply highly specialist scientific skills and expertise to lead in the delivery of high quality research and the preparation of high-impact research publications. 
  • To keep abreast of current developments in this research area. 
  • To report research progress to the supervisory team, the Cancer Institute, and at scientific conferences and meetings. 
  • To work with other Scientists within the team as necessary. 
  • To work safely by adhering to all University policies and practices, including preparing and following laboratory risk assessments, and complying with Health and Safety policies, ethical approval processes and Human Tissue Act guidelines. 

Analytical and Judgement Skills 

  • To demonstrate a high-level of technical and analytical skill to resolve highly complex scenarios, requiring analysis, interpretation and expert judgement to find the most appropriate solutions. 
  • To identify, interpret and integrate information from a wide variety of sources, and critically evaluate the quality and assumptions of these data. 
  • To show initiative and the ability to make decisions in areas where no previous work has been undertaken. 
  • To show awareness of your own developmental needs and undertake appropriate training where appropriate. 
  • To comply with professional codes of conduct. 
Research environment

The UCL Cancer Institute is a state-of-the-art institute to consolidate cancer research at UCL and promote links with our partner teaching hospitals, in order to support excellence in basic and translational studies. The Institute draws together talented scientists who are working together to translate research discoveries into developing kinder, more effective therapies for cancer patients. It is a Cancer Research UK and Experimental Cancer Medicine Centre, and contains approximately 580 staff, including 80 PhD and MD (Res) students and 30-40 MSc students. Core facilities within the Institute include: Genomics Facility (gene expression microarrays); Proteomics Facility; Imaging and Cell Sorting (confocal, time-lapsed microscopy, MoFlo FACS); Pathology Suite (laser capture microdissection, tissue arrays); Experimental Imaging (with UCL Institute of Child Health); and Transgenesis. 


Application

APPLICATIONS CLOSED (Monday 11 January 2021 17:00 (GMT)

Students will need to qualify as UK/EU fee payers and meet UCL general admissions criteriaThis studentship is subject to confirmation of funding from CRUK

To apply for this studentship, you must submit only three documents. 

  1. Your full CV including a short summary (<500 words) detailing how your experience and ability matches the project and the person specification. 
  2. A single PDF file containing scans of two academic references, and the transcripts of your university degree(s) showing your unit/module marks
  3. An equal opportunities monitoring form (Word download). This form will be separated from your application before it is forwarded to shortlisters. By submitting this form you are giving us consent to use the data contained for quality and monitoring purposes. Data will be anonymised.  . 

These three documents should then be emailed to ci.scholarships@ucl.ac.uk. Please write 'CRUK 2003 Hadjur' in the subject line of the email. 

APPLICATIONS CLOSED (Monday 11 January 2021 17:00 (GMT)