N-glycosylation sites in V-region of follicular lymphoma immunoglobulin and their role in lymphoma initiation.
|Funded by:||Pathological Society of Great Britain and Ireland||Stipend:||£15,863 p/a (MRC 2014 rate)|
|Start date:||From June 2015||Duration:||3 years|
|Location||Centre for Haemato-Oncology|
|Deadline:||30 April 2015|
This project designed to determine whether the introduction of N-glycosylation motifs in immunoglobulin is an early or late mutational event in FL. The student will investigate whether changes in immunoglobulin N-glycosylation are associated with specific mutation repertoire in FL. The student will assess whether the presence/number of N-glycosylation motifs influence the composition of the tumour microenvironment or associate with clinical outcome.
Who should apply:
Follicular lymphoma (FL) is an indolent B-cell malignancy representing a substantial cancer burden with thousands of new cases each year in the UK. While the introduction of immune chemotherapy has seen improvements in disease management overall, FL is considered largely incurable, with patients living in long term remission with the prospect of impending relapse and transformation to more aggressive disease. Our molecular profiling studies have postulated the existence of a genetically diverse ancestral pool of B cells, called the common progenitor cell (CPC) (Montoto et al. J Clin Oncol. 2011), which seems capable of evading treatment and propagating new episodes of the FL.
We are keen therefore to characterise events arising within this CPC population that parallel existing studies researching genetic changes within this progenitor compartment (Okosun et al., Nature Gen 2014). Our study sets out to revisit an observation demonstrating a novel way of interaction between FL cells and the tumour microenvironment (Zhu, D et al., Blood, 2002, Coelho, V et al., PNAS, 2010). This interaction is mediated by N-glycosylation motifs (N-X-S/T), introduced in VH/VL of the surface immunoglobulin (Ig) of FL B Cell Receptor as part of the normal somatic hypermutation (SHM) processing, and lectins from the innate immune system. These acquired motifs, unlike the N-glycosylation motifs of the constant region of Ig heavy chain that exist on every B cell, do not have mature carbohydrates but instead preferentially add high-mannoses – a target for mannose binding lectins. This unique cellular bridge is rare in normal B-cells from healthy individuals, but seems to be a feature of virtually all FL cases. If these glycosylation motifs are already laid down in the CPC population, they could represent a means of targeting these cells by abrogating the CPC-microenvironment interaction.
For an informal discussion, please contact the second supervisor: Sergey Krysov telephone:0207 882 3816.
Support and Benefits
We implement a comprehensive support programme for our research students, providing training in a wide range of biomedical laboratory methods and other vital transferable skills. Our aim is to equip our students for a career in science and to make them attractive to a variety of potential employers.
We offer our students travel bursaries and grants to support students who are presenting at conferences and meetings.
The studentship is funded by the Pathological Society of Great Britain and Ireland and comes with a tax-free stipend of approximately £15,863 (MRC rates) per annum. It is open to UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the UK prior to the start of the studentship. University tuition fees (at the UK/EU level) will be met by the funding body.
- Graduates that have achieved at least an upper second-class honours degree in a relevant subject such as Medical Genetics.
- If English is not your first language IELTS score of 6.5 or equivalent
- The studentship is not open to non-EU nationals.
How to apply
You will need to provide:
- Completed PhD application form
- Statement of purpose
- Copy of transcripts (break down of marks)
- Copy of passport
- If applicable, proof of English proficiency
Please email the completed application form and all supporting documents to: Sergey Krysov
Deadline for applications is: 30th April 2015
Interviews will be held approximately 2 weeks after the closing date
Please ensure you provide all supporting documents, as we are unable to consider incomplete application forms. You must contact your referees directly to request references. They can send these seperately Sergey Krysov.
We will be contacting all candidates who are shortlisted for an interview by email.
|Tel:||+44(0) 207 882 3816|
|Tel:||+44(0) 207 882 2081|