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  Investigate the effect of sequestration of Plasmodium falciparum-infected red blood cells on endothelial cells and astrocytes of the blood brain barrier, in cerebral malaria


   Faculty of Natural Sciences

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  Dr S J Chakravorty  No more applications being accepted  Self-Funded PhD Students Only

About the Project

Project Description:

Sequestration of Plasmodium falciparum-infected red blood cells (PRBC) within the microvasculature of the brain is a characteristic feature of cerebral malaria. This is believed to have a direct pathological effect on the blood brain barrier (BBB), which is the specialised interface between the blood and the brain parenchyma. The BBB is a complex neurovascular unit composed of brain endothelial cells, astrocytes and pericytes. There is evidence to show that adhesion of PRBC to the BBB has a direct effect on BBB structure and function and has been linked to neurological sequelae. This study will investigate changes in human brain endothelial cells and astrocytes in response to PRBC cytoadherence and mechanisms involved in mediating these changes. These studies will be performed using human brain microvascular endothelial cells (HBEC) and human astrocytes grown in tandem in an in vitro co-culture model, using an advanced model of the BBB..
Our previous studies, revealed an inflammatory and pro-adhesive effect in endothelial cells, in response to PRBC. Recent studies in our laboratory have demonstrated that soluble factors, released by HBEC as a result of interaction with PRBC during sequestration, can induce functional changes in endothelial cells.
We are currently interested in investigating the effect of PRBC on the structure and function of HBEC and astrocytes, when cultured in tandem, with a view to understanding the underlying mechanisms involved. This may be a potential mechanism for the development of pathological changes in astrocytes that lead to the development of neurological sequelae.


Qualifications, Experience and Skills Open to science graduates (with, or who anticipate obtaining, at least 2.1 or equivalent in relevant biological subject in undergraduate degree)

Competency in word processing, excel and powerpoint at basic level
Good communication skills in oral and written presentation Masters degree in a related topic
Competency in word processing, excel and powerpoint at advanced level
Competency in statistical analysis
Working under aseptic cell culture facilities
Immunoassays
Attitude and Personality
Conscientious, motivated
Good time management
Ability to work independently
Flexible attitude to lab activities
Good teamwork
Good communication skills
Good interpersonal skills

Eligibility criteria Open to science graduates (with, or who anticipate obtaining, at least 2.1 or equivalent in relevant biological subject in undergraduate degree, or a Masters degree - subject to university regulations).Open to UK/EU students and overseas students. Students without English as first language must provide evidence that they meet English language requirement, e.g. with IELTS score of 6.0, with no less than 5.5 in any subsections.


Funding Notes

Open to fully self-funded students only. You must have access to your own funding for all tuition fees and living expenses either from your home country or your own finances.
Information regarding University tuition fees is available below.
http://www.keele.ac.uk/studentfunding/tuitionfees/ukeustudents-postgraduateresearchprogrammefees/pgr2016/
http://www.keele.ac.uk/studentfunding/tuitionfees/internationalresearchprogrammefees2015/
For guidance on living costs please see
http://www.keele.ac.uk/pgresearch/feesandfinance/livingcosts/

Source of funding Self.

Terms and conditions of studentship As per the University Code of Practice

References

References:
Grab DJ, Chakravorty SJ, van der Heyde H, Stins MF. 2011. How can microbial interactions with the blood-brain barrier modulate astroglial and neuronal function?. Cell Microbiol, vol. 13(10), 1470-1478.
Maier AG, Rug M, O'Neill MT, Brown M, Chakravorty S, Szestak T, Chesson J, Wu Y, Hughes K, Coppel RL, Newbold C, Beeson JG, Craig A, Crabb BS, Cowman AF. 2008. Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell, 134(1), 48-61.
Chakravorty SJ, Hughes KR, Craig AG. 2008. Host response to cytoadherence in Plasmodium falciparum. Biochem Soc Trans, vol. 36(Pt 2), 221-228.
Jenkins N, Wu Y, Chakravorty S, Kai O, Marsh K, Craig A. 2008. Plasmodium falciparum ICAM-1-based cytoadherence-related signalling in endothelical cells. Journal of infection, vol. 56(4), 299.
Chakravorty SJ, Carret C, Ivens A, Nash GB. 2007. Altered phenotype and gene transcription in endothelial cells, induced by Plasmodium falciparum-infected red blood cells: Pathogenic or protective? International Journal for Parasitology, vol. 37(8-9), 975-987.
http://www.keele.ac.uk/lifesci/people/srabastichakravorty/