Dr Nicola J. Royle

Senior Lecturer

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Adrian building
Office: G19B, Lab G19

Department of Genetics
University of Leicester
University Road
Leicester, LE1 7RH

Tel: +44 (0)116 252 2270

Fax: +44 (0)116 252 3378

Email: njr@le.ac.uk

Personal details

  • B.Sc. Genetics and Cell Biology (Manchester)
  •  Ph.D. Genetics (Reading)

 

Websites

 

Teaching

I convene and teach on modules in biological sciences that have a particular focus on genes, inheritance, human genetics, genomics and disease.

 

Other responsibilities

  • Chair of Department’s Research Team
  • Member of College Research Committee
  • Member Early Career Researcher Development Group (ECRDG)
  • Academic Lead Departmental Cell Culture Facility

 

Research

My group is interested in cellular processes that impact on the length and stability of telomeric DNA in somatic cells and in the germ line.

Telomeres cap the ends of chromosomes and thus play an essential role in the maintenance of genome stability and cancer avoidance.

Some species use telomere shortening to regulate the number of cell divisions a cell can undergo before becoming senescent. Hence in humans, telomeres shorten with increasing age.

Sarcomas and the ALT mechanism

Sarcomas
Sarcomas and the ALT mechanism

Cancer cells maintain telomere length and thus overcome the senescence barrier. Most tumours do this by activating telomerase, but a significant minority activate another pathway called ALT (Alternative lengthening of telomeres).

We were one of the first groups to shown that the molecular basis of the ALT mechanisms involves a recombination-like process, though the details of the ALT mechanism and how it is activated are still poorly understood.

We are conducting research to identify genes that play important roles in the ALT mechanism. Interestingly a large proportion of human sarcomas activate the ALT mechanism but it is unclear why.

We want to determine whether this aspect of sarcoma biology can be exploited for diagnostic or therapeutic purposes.

HHV6 integration at telomeres

HHV6The two species of human herpes virus 6 (HHV-6A and -6B) are double-stranded DNA viruses ~160kbp in length and terminated by 8kb direct repeats that contain sequences homologous to human telomeric DNA. HHV-6 is unique among human herpesviruses as it can insert into the telomeric DNA of human chromosomes and this may represent an alternative form of viral latency. Once integrated it can be inherited from parent to child. Approximately 1% of the UK population carry an integrated copy of HHV-6 (CI-HHV-6) but it is not known whether this impacts on their health in the long term.

My group is investigating the relationship between CI-HHV-6 and telomere homoeostasis. We have shown that the viral genome can be truncated, circular molecules released and that the telomere on the end of the virus is often short.

We propose that the presence of the integrated HHV-6 genome interferes with telomere-loop formation and that this may facilitate the release of the viral genome from the telomere and so represent the first step towards viral reactivation.

This work has involved collaboration with Martin Dyer (Cancer Studies and Molecular Medicine). Click here to read the article online.

 

Telomeres, replication and DNA mismatch repair

Replication Fork
Replication Fork

We are also interested in problems associated with replication of telomeric DNA. We have exploited sequence variation within human telomeric DNA to investigate mutations that arise, for example, as a result of unusual G-quadruplex structures formed during replication of telomeric DNA.

We have shown that DNA mismatch repair (MMR) is required for stability of telomeric DNA and we are investigating the impact this may have on telomere length homeostasis. Inheritance of a mutated MMR gene in families results in predisposition to cancer, in particular, colon cancer (known as HNPCC or Lynch syndrome). We want to find out how telomere instability, driven by a deficiency in MMR, contributes to Lynch syndrome.

Chromatin organisation and telomere function
Telomere Function
Telomeres and lamins

Mammalian DNA is packaged with histones and other proteins into chromatin. Epigenetic modification of particular amino acids in histones and methylation of cytosine residues at CpG di-nucleotides in DNA affects the structure and function of the chromatin. We are characterising epigenetic changes that affect human telomere function and in collaboration with Dr Shackleton (Department of Biochemistry) we are also exploring the relationship between human telomeres and nuclear lamins.

Research Links

Search PubMed at the US National Library of Medicine for this author: http://www.ncbi.nlm.nih.gov/pubmed?term=Royle+NJ
Search Leicester Research ArchiveDr N. Royle
Search Google ScholarDr N. Royle

 

Supervision

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Contact Details

Department of Genetics
University of Leicester

Adrian Building
University Road
Leicester
LE1 7RH
United Kingdom

Tel: +44 (0)116 252 3374
E Mail: genetics@le.ac.uk

Head of Department
Professor Alison Goodall

Accessibility

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