Barbara Mawer Visiting Fellowship

2008 Award

The award is intended to support working laboratory visits by BRS members for periods of up to 2 months, either in the UK or overseas. The maximum value of the award, which can be made either to a single researcher or be shared between two or more individuals, is £3,000.

Applicants should email a brief description of the proposed work, reasons for the visit and estimated expenses to Colin Farquharson.

Awardees will be asked to submit a report on completion and to make a brief presentation to the BRS annual meeting; acknowledgement of the BRS in resulting publications will be required.

The deadline for applications is 6 June 2008. The successful applicant(s) will be announced at the BRS AGM in Manchester on 25 June 2008.

Recipient 2007

Host Centre

The Botnar Research Centre (Dr Philippa Hulley)
Oxford Institute of Musculoskeletal Sciences
Oxford University
Windmill Road
Headington, Oxford
OX37LD
UK
Email: [email protected]

Project Proposal

Supra-physiological doses of glucocorticoids directly affect bone, decreasing osteoblast number and bone formation and this is in part due to promotion of osteoblast apoptosis[1-3]. However, the critical signalling intermediates in glucocorticoid-induced apoptosis remain largely undefined.

I am currently studying the role of different members of the Bcl-2 family of mitochondrial proteins as mediators of glucorticoid -induced apoptosis in osteoblastic cells. In particular I have investigated the pro-apoptotic protein Bim, which has been reported to be an initiator of apoptosis in different models of hematopoietic cells in vitro[4, 5]. In osteoblastic cells I have described that Bim is upregulated in response to dexametasona treatment and that correlates with the index of apoptosis in these cells. This same pattern of expression of Bim was also observed in primary human bone cells (work in progress).

In order to show the causality of this pro-apoptotic protein Bim I wish to use siRNA (small interference RNA) technology. SiRNA will allow me to demonstrate in vitro whether Bim expression is necessary for dexametasone apoptosis in this particular type of cells.

Dr Hulley´s group at the Botnar Research Centre (Oxford, UK) have gained considerable experience working with an osteoblastic cell line (MBA 15.4) which is sensitive in terms of apoptosis to glucocorticoid treatment and therefore represents a suitable model for studying the effects of these drugs. Importantly, Dr Hulley´s group now has experience using siRNA technology with this cell line. In order to progress my own research it would be extremely useful to spend a research period in Oxford learning this technique; this could then be applied to my cell line.

I would like to apply for a visiting fellowship to Oxford, for a period of two months. Dr Philippa Hulley has kindly agreed to receive me for the purpose of the visit. Expenses required are detailed below.

Expenses Requested

Living expenses per month: 800 pounds
Return flight Santander-London: 200 pounds

Total expenses for two months: 1800 pounds

References

1. Weinstein, R.S., et al., Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest, 1998. 102(2): p. 274-82.
   
2. Abu, E.O., et al., The localization of the functional glucocorticoid receptor alpha in human bone. J Clin Endocrinol Metab, 2000. 85(2): p. 883-9.
   
3. Eberhardt, A.W., A. Yeager-Jones, and H.C. Blair, Regional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid- treated rabbits. Endocrinology, 2001. 142(3): p. 1333-40.
   
4. Bouillet, P., et al., Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity. Science, 1999. 286(5445): p. 1735-8.
   
5. Wang, Z., et al., Microarray analysis uncovers the induction of the proapoptotic BH3-only protein Bim in multiple models of glucocorticoid-induced apoptosis. J Biol Chem, 2003. 278(26): p. 23861-7.

   
   

    

    

Updated: 17-apr-08

© 2006  The Bone Research Society - Secretary: Dr Colin Farquharson