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Bioengineering bone models for high throughput cancer drug screening


Faculty of Biological Sciences

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Dr Mahetab Amer Applications accepted all year round Self-Funded PhD Students Only
Leeds United Kingdom Bioengineering Biomechanics Biophysics Cancer Biology Cell Biology Pharmacy Polymers Tissue Engineering

About the Project

Cell behaviour is regulated by three-dimensional (3D) cell-cell and cell-matrix interactions with its microenvironment. Our understanding of how certain aspects of the bone microenvironment promote survival and proliferation of cancer cells in bone remains poor, partly due to a lack of clinically relevant model systems which recapitulate human spatial and temporal signals within the bone microenvironment. Biomaterials have been of great interest in tissue engineering to recreate aspects of the dynamic 3D bone environment.They can provide 3D support for cell growth, allow basic discovery research into regeneration mechanisms and provide drug screening models. Biomaterials can also be modified and functionalized to present certain cues to mimic different environments. Mechanical, chemical and topographical properties can be engineered and altered to help direct stem cell fate for a desired outcome or to promote cell maintenance/expansion. Our recent work has demonstrated how mesenchymal stromal cells can be supported using topographically textured microparticles, which may be functionalised with specific chemistries, to mimic aspects of the bone niche. This 3D niche model can be used to influence MSC attachment, function and fate, and help promote the maintenance of other cell types, such as HSCs, in the lab. 

The main aim of this multidisciplinary PhD project is to develop customisable, mineralised micromodels of bone to explore the bidirectional 3D cell-cell and cell-matrix interactions within bone/bone marrow niches. These models will have precisely tuned mechanical environments and will contain varying patterns of matrix-inspired and cellular cues.

The successful candidate will be based at the School of Molecular and Cellular Biology (Faculty of Biological Sciences) at the University of Leeds. You will work under the supervision of Dr Mahetab Amer (https://biologicalsciences.leeds.ac.uk/biological-sciences/staff/1527/dr-mahetab-h-amer), working at the interface of tissue engineering and cell biology. The findings will establish improved approaches for studying the pathogenesis of bone cancer and for developing high-throughput models to test new therapies. 

The PhD project will integrate a range of approaches including tissue engineering and 3D cell culture techniques, materials chemistry, molecular analysis, and advanced imaging. This will be used for qualitative and quantitative evaluation of the interactions between cells and their extracellular matrix, and how physicochemical properties of bone matrix may favour tumour cell seeding in bone. 

Requirements: This is a PhD suitable for an individual with drive and enthusiasm for working at the interface of physical sciences and cancer biology, and is particularly suited to those with an interest in multidisciplinary, translational research. Cell culture experience would be highly advantageous. You will be able to access state-of-the-art facilities in vibrant laboratory settings. The student will be trained on tissue engineering-based methodologies, such as 3D cell culture, biomaterials fabrication, characterisation of cell-material interactions and biological/physical cues that drive cell response. 

Eligibility 

You should hold a first-degree, equivalent to at least a UK upper-second class honours degree, or a MSc degree in a relevant subject. This project would suit someone with a strong background in tissue engineering, cancer biology or closely-related areas. Additional experience of conducting research in a multidisciplinary setting is highly desirable. Upon completion of the PhD, the successful candidate will be uniquely equipped for high-demand careers within academia or industry with desirable skills in bioengineering, regenerative medicine and cancer cell biology. 


References

 Amer, M., Alvarez-Paino, M., McLaren, J., Pappalardo, F., Trujillo, S., Wong J., Shrestha, S., Abdelrazig, S., Lee, JB, Stevens, L., Kim, D, Gonzalez-Garcia, C., Needham, D., Salmeron-Sanchez, M., Shakesheff, K., Alexander, M., Alexander, C., Rose, F. “Designing topographically textured microparticles for induction and modulation of osteogenesis in mesenchymal stem cell engineering”; Biomaterials, 266, 120450 (2021)
 Abu Awwad, H., Thiagarajan, L., Kanczler, J., Amer, M., Bruce, G., Lanham, S., Rumney, R., Oreffo, R., Dixon, J. “Genetically-programmed, mesenchymal stromal cell-laden & mechanically strong 3D bioprinted scaffolds for bone repair”, Journal of Controlled Release, 325, 335 (2020)
 Prina, E., Amer, M.*, Sidney, L., Tromayer, M., Moore, J., Liska, R., Bertolin, M., Ferrari, S., Hopkinson, A., Dua, H., Yang, J., Wildman, R., Rose, F. “Bioinspired precision engineering of three‐dimensional epithelial stem cell microniches”. Advanced Biosystems, 4, 2000016 (2020)
 Alvarez-Paino, M., Amer, M.*, Nasir, A., Cuzzucoli Crucitti, V., Thorpe, J., Burroughs, L., Needham, D., Denning, C., Alexander, M., Rose, F., Alexander, C. “Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function". ACS Applied Materials & Interfaces, 11, 34560 (2019)


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