School of Engineering and Materials Science Research Studentships
Development of an organ-chip to study regulation of primary cilia mechanobiology as novel treatment of Polycystic Kidney Disease
Supervisors: Martin KNIGHT
Application Deadline: 31-01-2021
This studentship provides an exciting opportunity to join a team of biomedical scientists and bioengineers using organ-chip technology to investigate primary cilia and test new therapies. The project will test the hypothesis that pharmaceutical elongation of primary cilia in kidney epithelial cells enhances essential mechanotransduction. The student will examine whether this can compensate for the genetic disruption of cilia that causes Polycystic Kidney Disease (PKD).
Prof Knight’s group have a long track record of studying the role of primary cilia in mechanobiology. In the kidney it is thought that epithelial primary cilia bend in response to the flow of urine and that this triggers a mechanotransduction pathways necessary for healthy kidneys. Studies suggest that changes in primary cilia length increase mechano-sensitivity thereby providing a potential ‘ciliotherapy’ strategy for treatment of PKD.
We have recently conducted a high-throughput confocal imaging screen and identified a cluster of compounds that cause primary cilia elongation in cartilage cells and may therefore be repurposed as a novel treatment for PKD.
The research will be conducted in the Queen Mary+Emulate Organs-on-chips Centre (www.cpm.qmul.ac.uk/emulate/), supported by our Centre Scientist and integrating within a large team of post docs and PhD students supervised by Prof Martin Knight and Dr Cleo Bishop. The student will also be integrated with the internationally-leading research being conducted at Queen Mary University of London in the Centre for Predictive in vitro Models (www.cpm.qmul.ac.uk), the Division of Bioengineering in the School of Engineering and Materials Science (www.sems.qmul.ac.uk/research/bioengineering) and the Blizzard Institute in the School of Medicine and Dentistry (www.qmul.ac.uk/blizard).
The project will be broken down into a series of work packages as follows:
- The student will first characterise the effect on kidney epithelial primary cilia of compounds that we have found to elongate cilia in cartilage cells. This work will involve high-throughput confocal screening and automated analysis performed using InCarta 3D analysis software and the IN Cell microscope managed by Dr Bishop.
- The student will then test the effect of cilia elongation on epithelial response to fluid shear using both the Flexcell fluid flow bioreactor system and the Emulate kidney-chip
- The project will examine the effect of cilia elongation on the cilia mechanosignalling pathways including the activation of mechanosensitive polycystin Ca2+ signalling following protocols well-established in Knight’s group.
- The student will next develop the PKD organ-on-a-chip using a validated kidney-chip developed by our industrial partner Emulate Inc. This PKD-chip with initially use epithelial cells treated with siRNA to Pkd1/2 or cells isolated from PKD animal models.
- Finally the student will test whether compounds that elongate epithelial cilia and regulate mechanosignalling can rectify the dysfunction in ciliary structure and mechanosignalling in PKD cells and can prevent cyst formation within the validated PKD-chip
EPSRC Research Studentship Details
To be eligible for a full award (stipend and fees) applicants must have:
- settled status in the UK, meaning they have no restrictions on how long they can stay and
- been ‘ordinarily resident’ in the UK for 3 years prior to October 2021.This means they must have been normally residing in the UK (apart from temporary or occasional absences and
- Not been residing in the UK wholly or mainly for the purpose of full-time education (This does not apply to UK nationals).
(See: https://epsrc.ukri.org/skills/students/help/eligibility/ for more details)
- Full Time programme only.
- Applicant required to start in September 2021.
- The studentship arrangement will cover tuition fees and provide an annual stipend for up to three years (Currently set as £17,285 in 2020/21).
- The minimum requirement for this studentship opportunity is a good Honours degree (minimum 2(i) honours or equivalent) or MSc/MRes in a relevant discipline.
- If English is not your first language you will require a valid English certificate equivalent to IELTS 6.5+ overall with a minimum score of 6.0 in Writing and 5.5 in all sections (Reading, Listening, Speaking).
Supervisor Contact Details:
For informal enquiries about this position, please contact Prof Martin Knight
To apply for this studentship and for entry on to the Medical Engineering programme (Full Time) please follow the instructions detailed on the following webpage:
Research degrees in Engineering:
Further Guidance: http://www.qmul.ac.uk/postgraduate/research/
Please be sure to include a reference to ‘2021 SEMS EPSRC DTP MK’ to associate your application with this studentship opportunity.