Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).
This 4-year PhD studentship is offered in Dr Dominique Bonnet’s Group based at the Francis Crick Institute (the Crick).
Human bone marrow tissue is a complex interactive highly vascularized structural system with distinctitive niches that provide support to the HSPCs [1]. There is ample published data suggesting the existence of anatomical gradients across the bone marrow tissue, with each niche having distinctive role, and the biophysical gradations linking these niches. Mimicking the bone marrow niche as a coordinated entity of action requires understanding the HSPC fate decisions in response to multiplexed cellular components, biophysical, and biomolecular signals. Efforts to understand these signals has been mainly impeded by the lack of reliable ex vivo models that can emulate the human bone marrow structure. The aim of the project is to create an innovative bioenginnered fully humanised 3D in vitro model of the bone marrow microenvironment that will enable us study both normal and malignant haematopoiesis. We have recently developed a 3D humanised ossicles in vivo [2, 3] system, that has allowed us to reliably study the cross-talk between the human bone marrow niche components and haematopoietic stem cells, as well as evaluate the alterrations that are induced during leukemic development. Although, this in vivo humanized ossicle model allows us to perform long term experiments (>6 weeks), however there are some limitations for example serial sampling of the cells (or secretory factors), feasibility of performing short-term experiments, large scale drug testing and the need to use mice, that are known to be associated with high costs.
We have recently generated in vivo data (unpublished) using confocal microscopy that has allowed us to map the structural architecture of the bone and the associated vasculature which is known to be crucial in HSPC maintenance and proliferation. Combining this microscopy data with various mathematical modelling tools has enabled to create a detailed map of the bone marrow vasculature system and this available data can be used to print structures using a 3D bioprinter. We will also use various available bio-inks to mimic (and advanced biodegradable hydrogels) and recapitulate the mechanical properties of the BM. Our in vitro model will be based entirely on 3D bioprinting the structure to mimic BM niche architecture.
Our proposed in vitro model will allow us to study the secretory factors (such as cytokines) and niche component(s) that could be responsible for maintaining normal stem cells, induce their differentiation as well as monitor the elements that mediate the HSPCs mobilization out of the niche(s). This system will also enable us to understand the mechanisms of leukaemoneogenesis and test the drugs
Candidate background
I am particularly interested in receiving applications from candidates with a background in stem cell biology, and molecular biology. An individual being familiar with flow cytometry analysis and/or bioengineering will be a plus.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
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