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Pre- Approved Projects

Pre-Approved Projects available

Some projects are already approved. Have a look below!

If you don't find a project that suits your interests, you can directly contact our supervisors to talk about the research they are doing and design a project with them.

Biomedical Sciences Pre-Approved Projects:

Mode of Study

Full-Time

Eligibility

Home/EU/OS

Supervisors

Darius Koester, Anne Straube

Project summary

Ehlers-Danlos Syndromes are a group of 13 hereditary connective tissue disorders characterized by tissue fragility and laxity Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common form the EDS with an approximate incidence of 1-500. It primarily affects the joints causing joint instability and chronic pain. Little is known about the pathogenesis of hEDS. Fibroblast cells derived from patients with hEDS show an abnormal integrin expression. a class of transmembrane proteins that link the cell cytoskeleton to the extracellular matrix (ECM). This alters the way fibroblasts bind to the ECM, how mechanical forces are transmitted and the mechano-signalling of cells. Interestingly, hEDS fibroblasts were shown to express elevated levels of α-smooth muscle actin (α-SMA) compared to normal fibroblasts which is associated with a transition to the more contractile myofibroblasts. While trans-differentiation of fibroblast to myofibroblast is a complex process the mechanical properties of the ECM are an important influence on it.

We will test how the mechanical properties of the wildtype and hEDS ECM affect fibroblast contractility and vice versa, how wildtype or hEDS fibroblasts affect and remodel the ECM.Using protocols developed in the Koester lab, we will derive ECM from wildtype and hEDS fibroblasts and study their ultrastructure using electron microscopy as well as test its mechanical properties using AFM.

To study the dynamic interplay of cells and ECM using our state-of-the-art confocal microscope combined with an atomic force microscope (AFM). We will seed (wildtype or hEDS) fibroblasts within ECM (wildtype or hEDS) and visualise dynamics of cell cytoskeletal components (fluorescently labelled actin, microtubules, integins) using confocal fluorescence microscopy while testing the mechanical properties of the ECM-cell composite using AFM.

In a second part, we will test the idea that changes in the mechanical properties of the ECM-cell composite in hEDS causes mast cell activation syndrome, due to mechanical stimulation of mast cells leading to degranulation.Mast cells will be seeded together with wildtype and hEDS fibroblast ECM composites, and their activation monitored over time or before and after global mechanical stimulation by stretching the cell-ECM composite.

Methodology

  • Culture of fibroblast cell lines is established in the lab, and ECM can be derived from these cell lines by simply adding ascorbic acid to the medium
  • For fluorescence microscopy, cell components are either labelled by fixation and immunofluorescence or by expressing fluorescently labelled marker proteins (e.g. lifeact-mRuby, integrin-alpha1-GFP…
  • An important element will be atomic force microscopy combined with confocal fluorescence microscopy on our new BioAFM
  • For the measurement of cell contractility, we will perform traction force microscopy by seeding cells on soft, PDMS substrates containing tracer particles
  • To generate patterned substrate with defined regions of cell adhesion sites we will use the new Primo2 micropatterning device.

Please ensure that you specify the name of the project and supervisor within your application

No suitable project?

If none of the projects available are suitable, you should approach one of the approved supervisors and develop a project together.

The supervisor will need to get the project approved by the Research Degrees Team.

The list of approved supervisors in Biomedical Sciences and their research interests can be found here.

Applied Health Pre-Approved Projects:

Please ensure that you specify the name of the project and supervisor within your application

No suitable project?

If none of the projects available are suitable, you should approach one of the approved supervisors and develop a project together.

The supervisor will need to get the project approved by the Research Degrees Team.

The list of approved supervisors in Applied Health and their research interests can be found here.

Clinical Trials Unit (CTU) Pre-Approved Projects:

Coming soon!

You can contact potential supervisors to develop your own PhD project:

Have a look at the CTU supervisors and their research here.