Human stem cell models of de novo tumorigenesis to replace the use of animals for the study of cancer initiation
A PhD studentship in stem cell biology and disease modelling is available in Dr Allegrucci’s group (www.nottingham.ac.uk/vet/people/cinzia.allegrucci) at the Biodiscovery Institute, University of Nottingham.
The project aims to develop a novel gene edited human pluripotent stem cell model to study Triple Negative Breast Cancer (TNBC). TNBC represents the most aggressive breast tumour subtype, with no effective targeted therapies available. Progress is further hindered by TNBC heterogeneity as TNBC is also a not a single disease, but further subdivided into distinct molecular and clinical subtypes based on specific molecular pathway signatures and mutational landscapes that impact on patient outcome. To date, the identification of biomarkers of TNBC initiation that can be used for early detection and treatment of TNBC patients remains an unmet clinical need. This project will develop a novel way to investigate the function of specific genetic mutations in the initiation of TNBC, which will replace the use of genetically engineered and xenograft mouse models. To this end, we will introduce genetic changes associated with TNBC into normal induced pluripotent stem cells (iPSC) made for mammary cells to recreate the development of cancer in an in vitro 3D breast organoid model that will use synthetic hydrogels to provide a superior matrix not derived from animal tumours to study interaction of tumour cells with their environment. Importantly, this advanced cell model provides advantages over other cancer patient-derived cultured cell systems as it allows modelling cancer initiation which is critical for the development of therapeutic strategies to target early-stage disease and improve patients’ survival.
Training will be provided in cutting-edge techniques including CRISPR/Cas9 gene editing, iPSC disease modelling, 3D organoid culture, omics and bioinformatics approaches for the definition of the molecular mechanisms involved in cancer initiation, and 3Rs methods.
More information can be found at https://www.nc3rs.org.uk/human-stem-cell-models-de-novo-tumorigenesis-replace-use-animals-study-cancer-initiation.
Further information and Application:
1) Candidates should complete an online application found at www.nottingham.ac.uk/pgstudy/how-to-apply/apply-online.aspx.
2) Please email a CV along with a covering letter stating why you are interested in the project and how your attributes and skills align with the project goals to [Email Address Removed]. You are guided to complete this step as soon as possible.
Closing date: The position will be filled when suitable candidates have been identified. Early application is strongly encouraged.
Start Date: April/July 2022 or as soon as possible thereafter.
Entry requirements: A high 2.1 or 1st class degree in a relevant biological degree. This exciting project requires a motivated and inspired candidate with a forward thinking, positive, can-do attitude and a strong interest in the 3Rs principles.
Eligibility for Funding: This is a 4 -year studentship fully funded for UK candidates by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). International candidates are eligible to apply, however they would need to fund the difference in tuition fee.