Skip to main content

A novel human 3D in vitro dynamic model with integrated sensors for studying neurovasculature inflammation

PGR-P-613

Key facts

Type of research degree
PhD
Application deadline
Thursday 30 April 2020
Project start date
Sunday 1 November 2020
Country eligibility
International (open to all nationalities, including the UK)
Funding
Funded
Source of funding
University of Leeds
Supervisors
Dr Virginia Pensabene and Dr Sikha Saha
Additional supervisors
Paolo Actis, Gin Jose
Schools
School of Electronic and Electrical Engineering
Research groups/institutes
Pollard Institute
<h2 class="heading hide-accessible">Summary</h2>

The brain microvasculature is composed of endothelial cells, pericytes and astrocytes. The endothelium forms the barrier between the blood and the brain cells (i.e &quot;blood-brain barrier&quot;, BBB). Inflammation has been shown to disrupt the stability of the BBB and to initiate the atherosclerosis, neurodegenerative diseases, such as Alzheimer's disease (AD). AD is associated with cognitive decline and accumulation of amyloid beta peptides (A&beta;) in the brain. The BBB maintains the brain homeostasis. A&beta; plays significant roles in the BBB dysfunction. Conversely, BBB dysfunction leads to faulty A&beta; clearance from the brain and increased influx of peripheral A&beta; across the BBB (Sagare et al.,2012). Thus, it is imperative to study the mechanisms of BBB dysfunction in a physiologically relevant model for developing better therapeutic strategy targeting BBB integrity for this devastating disease. At present, most studies on BBB use complex in vivo models in mice and dogs. In vitro models are primarily based on 2D constructs, use animal cells and lack the shear stress produced by blood flow. Organs-on-a-chip platforms are often intricate, laborious and do not allow to visualize cell-cell interaction across the BBB (Brown &amp; Pensabene, 2015). Collaborating with Kirkstall Ltd and Queen Mary University of London, supported by BBSRC/Innovate UK, we recently optimised human primary cell densities, flow rate for individual cell types and conditioned-medium for growing BBB cell types together using Quasi-Vivo system (QVS). We thus showed that A&beta; produces differential effects on BBB cells under static and dynamic conditions (Miranda-Azpiazu et al.,2018). Novelty: This PhD project aims to develop a reliable microphysiological system (MPS) or Organ-on-a-chip (OOAC) system recreating the hematoencephalic barrier to clarify the role of endothelial inflammation, the effects of A&beta; and other pro-inflammatory cytokines on individual and co-cultured human cells to understand the downstream mechanisms of these proteins on BBB under dynamic condition. By integrating laser, nanoparticles for selective imaging and nanofluidic sensors in the microfluidic system, it will be possible for the first time to directly and non-invasively monitor the cell behaviour and response to a therapeutic treatment.

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

<p>The student will be trained by Pensabene on microfluidic system and join Pensabene&#39;s team working on a microfluidic platform developed and supported by NC3Rs. In order to develop the microfluidic system and to integrate sensors, the student will need access to the clean room and to the bionanoelectronics lab in the School of Electronic and Electrical Engineering.</p> <p>The cell culture work will take place primarily in the LICAMM, which is fully equipped to perform the proposed experiments. All methodologies (e.g., dynamic cell culture, immunohistochemistry, ELISAs, Real-time PCR and Western blotting) to be used are established in the Saha laboratory. Saha is currently supervising 4 PhD students (one with Pensabene) and 2 PDRAs with Jose. The student will be trained on laser sensors in Gin Jose&rsquo;s Lab (Jose is supervising 4 PhD students and 5 postdocs) and on nanopipette sensing by Paolo Actis (Actis coordinates an EU ITN network, co-supervises a PhD student and shares lab space with Virginia Pensabene).</p> <p>The applicants are members of the Leeds Cardiovascular Research Centre, which promotes collaborative working through a variety of means including an annual research retreat attended by many postgraduate students. The Institute is home to a BHF funded 4-year PhD programme, which includes a foundation year comprising lectures, small group teaching and laboratory skills sessions (e.g. cell culture, real time PCR, imaging, histology, statistics, and ethics). The student will join in with these elements of the programme and foster social and academic links with the wider cohort of PhD students.</p> <p>Pensabene along with Dr Saha, Actis&nbsp;and Jose will make up the supervisory committee. Specific training needs of the student will be discussed with the supervisors and an effective training plan will be agreed within one month of starting the PhD degree and recorded in the University Graduate Record system. Student will be provided with 3month Gantt chart to allow monitoring of progression. The plan will include clear and achievable targets, stating deadlines for completing different training activities including writing scientific report and thesis. Formal assessment, in the form of a <em>viva voce </em>examination, takes place at eighteen months after registration.</p> <p>Student will be coached for publications by the supervisors. Student will also attend personal and professional development courses/ opportunities offered by the University.</p>

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://eps.leeds.ac.uk/electronic-engineering-research-degrees/doc/apply">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &quot;A novel human 3D in vitro dynamic model with integrated sensors for studying neurovasculature inflammation&quot; as well as&nbsp;<a href="https://eps.leeds.ac.uk/staff/870/Dr_Virginia_Pensabene">Dr. Virginia Pensabene</a> as your proposed supervisor.</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> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

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

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

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

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<h2 class="heading">Funding on offer</h2>

<p>UK/EU/International&nbsp; &ndash; School of Electronic &amp; Electrical Engineering&nbsp;Scholarship Award paying Academic Fees at Home/EU fee rate&nbsp;of &pound;4,600 in Session 2020/21 or International fee rate&nbsp;of &pound;23,750 in Session 2020/21 and Maintenance matching EPSRC rates (currently &pound;15,009 in Session 2019/20) per year for 3 years.&nbsp;&nbsp;Funding is awarded on a competitive basis.</p>

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

<p>For further information regarding your application, please contact Doctoral College Admissions by email:&nbsp;<a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a>&nbsp;or by telephone:&nbsp; +44 (0) 113 343 5057.</p> <p>For further information regarding the project, please contact Dr Virginia Pensabene by email:&nbsp;&nbsp;<a href="mailto:V.Pensabene@leeds.ac.uk">V.Pensabene@leeds.ac.uk</a></p> <p>&nbsp;</p>


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