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Developing Blood Cell Production Platforms for Therapeutic Applications


Project Description

Generation and modification of blood cells ex vivo or in vitro harbours a huge potential in cell based therapies and regenerative medicine. An important bottleneck in realising this potential is the difficulty in efficiently producing large amounts of blood products in vitro. One way to address this problem is to find new ways to effectively manipulate blood precursors and progenitors to create cell lines that can be amplified while still retaining their developmental potential. These cells could potentially represent an unlimited source of therapeutically relevant cell products such as modified natural killer cells, chimeric antigen receptor T-Cells, modified red blood cells, platelets or haematopoietic stem cells. The seminal demonstration that pluripotency can be induced by the ectopic expression of specific transcription factors has instigated a lot of interest in developing new strategies to manipulate the developmental potential of cells. Transcription factor directed reprogramming, trans-differentiation, or induced proliferation have been achieved through ectopic gene expression. Novel non-genetic methods, such as protein transduction or use of chemical compounds, have been demonstrated as potential alternatives to genetic modification producing similar results, establishing a clinical path for new discoveries in gene based cellular modulation strategies.
This PhD project aims to establish modified blood cell platforms for applications in advanced cellular therapies. An ideal target to induce proliferation of is the haemogenic endothelium (HE), which is a rare transient cell population generated during embryonic development, and the precursor to all adult blood cells including haematopoietic stem cells (HSCs). The potential of modifying these HE and blood cell lines to produce customized blood cell products will be explored with the ultimate goal of developing new potential cellular immunotherapies for the treatment of cancer and autoimmune diseases.

Applications are invited from exceptionally high calibre students, graduates or final year undergraduates who have, or are expected to obtain a first or upper second class honours degree and who are highly committed to pursuing a PhD in cancer research.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk.

Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

Informal enquiries may be made directly to the primary supervisor.


References

-Pearson S, Cuvertino S, Fleury M, Lacaud G, Kouskoff V. In vivo repopulating activity emerges at the onset of hematopoietic specification during embryonic stem cell differentiation. Stem Cell Reports.; 2015;4:431–44.
-Lie-A-Ling M, Marinopoulou E, Li Y, Patel R, Stefanska M, Bonifer C, et al. RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence. Blood. 2014;124:e11-e20.
-Riddell J, Gazit R, Garrison BS, Guo G, Saadatpour A, Mandal PK, et al. Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell. 2014;157:549–64.
-Eliades A, Wareing S, Marinopoulou E, Fadlullah MZH, Patel R, Grabarek JB, et al. The Hemogenic Competence of Endothelial Progenitors Is Restricted by Runx1 Silencing during Embryonic Development. Cell Rep. 2016;15:2185–99.
-Cheng H, Ang HYK, El Farran CA, Li P, Fang HT, Liu TM, et al. Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors. Nat Commun. 2016;7:1-15.

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