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Development and characterisation of a novel human dynamic in vitro Blood Brain Barrier model to explore the effects of amyloid ? -peptide on the barrier integrity

PGR-P-230

Key facts

Type of research degree
4 year PhD
Application deadline
Ongoing deadline
Country eligibility
International (outside UK)
Funding
Non-funded
Supervisors
Dr Sikha Saha
Additional supervisors
Dr Virginia Pensabene, School of Electronic & Electrical Engineering, Faculty of Engineering, University of Leeds.
Schools
School of Medicine
Research groups/institutes
Leeds Institute of Cardiovascular and Metabolic Medicine
<h2 class="heading hide-accessible">Summary</h2>

Alzheimer‘s disease (AD), which is defined by memory deficits and cognitive impairment, is the most common form of dementia in the elderly with more than 26 million people worldwide living with the disease. AD is characterized, among other pathological features by the accumulation of beta-amyloid peptides (A? peptides) in the brain. A? peptides are thought to contribute to synaptic dysfunction and neuro-inflammation in the brain and play a significant role in the blood brain barrier (BBB) dysfunction during the course of AD. At present, there are not proper human in vitro blood brain barrier models, which mimic physiological human conditions, and the effects of each A? fragment on the individual BBB cells as well as BBB integrity remains unknown.

<h2 class="heading hide-accessible">Full description</h2>

<p>The main aim of this pilot project is to improve a novel human in vitro dynamic BBB model to examine the differential effects of specific A&beta; peptide fragments (e.g., A&beta; 1-40 and A&beta;25-35) in both static and dynamic conditions. We will focus on the effect of each fragment over each cell type implicated in the BBB formation and transport. This will help us to design further experiments to study the role of BBB implication in AD in a more realistic way, which could lead to the development of new therapies for this devastating disease. The student will get training on cell culture, microfluidic system, immunohistochemistry, Western Blotting, and other relevant techniques. The student will participate to weekly lab meeting and journal club to share their work with the group. The student will have advantage in working in a multidisciplinary environment and gain experience in presentation and publication of research work.</p> <h3>References</h3> <p>Pflanzner T, Kuhlmann CR, Pietrzik CU. Blood-brain-barrier models for the investigation of transporter- and receptor-mediated amyloid-beta clearance in Alzheimer&lsquo;s disease. Curr Alzheimer Res 2010 Nov;7(7):578-590.</p> <p>Zlokovic BV. Clearing amyloid through the blood-brain barrier. J Neurochem 2004 May;89(4):807-811.</p> <p>Gosselet F, Saint-Pol J, Candela P, Fenart L. Amyloid-beta peptides, Alzheimer&lsquo;s disease and the blood-brain barrier. Curr Alzheimer Res 2013 Dec;10(10):1015-1033.</p>

<h2 class="heading">How to apply</h2>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. To apply for this project applicants should complete a<a href="https://medicinehealth.leeds.ac.uk/downloads/download/129/faculty_graduate_school_-_application_form"> Faculty Application Form</a> and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School <a href="mailto:fmhgrad@leeds.ac.uk">fmhgrad@leeds.ac.uk</a>.</p> <p>We also require 2 academic references to support your application. Please ask your referees to send these <a href="https://medicinehealth.leeds.ac.uk/downloads/download/130/faculty_graduate_school_-_scholarship_reference_form">references</a> on your behalf, directly to <a href="mailto:fmhgrad@leeds.ac.uk">fmhgrad@leeds.ac.uk</a></p> <p>If you have already applied for other projects using the Faculty Application Form this academic session you do not need to complete this form again. Instead you should email fmhgrad to inform us you would like to be considered for this project.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p>

<h2 class="heading heading--sm">Entry requirements</h2>

A degree in biological sciences, dentistry, medicine, midwifery, nursing, psychology or a good honours degree in a subject relevant to the research topic. A Masters degree in a relevant subject may also be required in some areas of the Faculty. For entry requirements for all other research degrees we offer, please contact us.

<h2 class="heading heading--sm">English language requirements</h2>

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The Faculty of Medicine and Health minimum requirements in IELTS and TOEFL tests for PhD, MSc, MPhil, MD are: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • TOEFL iBT - overall score of 100 with the listening and reading element no less than 22, writing element no less than 23 and the speaking element no less than 24.

<h2 class="heading">Contact details</h2>

<p>For further information please contact the Graduate School Office<br /> e: <a href="mailto:fmhgrad@leeds.ac.uk">fmhgrad@leeds.ac.uk</a>, t: +44 (0)113 343 8221</p>


<h3 class="heading heading--sm">Linked research areas</h3>