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  (MRC DTP) Investigating leukaemia cellular heterogeneity and stem cell properties by single cell RNAseq technologies


   Faculty of Biology, Medicine and Health

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  Dr Syed Murtuza Baker, Prof Georges Lacaud, Dr Mudassar Iqbal  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by a block in differentiation and an accumulation of immature myeloid cells. Cytotoxic therapy has been the standard of care over the last 30 years for AMLs. Unfortunately, more often than not, it fails to cure the patient (5 years survival rate lower than 30%). Therefore, there is a pressing need for the development of more specific and efficient therapies. Bulk and single cell RNA sequencing have empowered researchers to quantify the global gene expression of populations and single cells to further understand the development, maintenance and treatments of cancers. The main aims of this project are to use state of the art single cell RNA-seq and bioinformatics to define the cellular hierarchy in MOZ and MLL gene rearranged leukaemia, to determine how these different cellular compartments are affected by drug/compound treatments and to identify genes critical for the maintenance of the most immature cell populations.

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/


Funding Notes

Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. Fadlullah MZH, Wen Hao N, Lie-a-ling M, Thambyrajah R, Patel R, Mevel R, Aksoy I, Savatier P, Baker SM, Rattray M, Kouskoff V, Lacaud G. Single-cell profiling of hemogenic endothelium and its surrounding niche in the mouse dorsal aorta. In Press Blood
MZH Fadlullah is a CRUK funded PhD student finishing this year, he was spending 3 days/week in Lacaud’s laboratory and 2 days/week in Barker‘s & Rattray’s laboratory. He has gained comprehensive training in interdisciplinary skills, combining in vitro and in vivo models of blood development (whole-organism physiology) and state of the art single-cell bioinformatics (quantitative skills).
2. Simeoni, F., Romero-Camarero, I., Camera, F., Amaral, F., Sinclair, O., Papachristou, E. K., Spencer, G., Lie-A-Ling, M., Lacaud, G., Wiseman, D., Carroll, J. S. & Somervaille, T. Enhancer recruitment of transcription repressors RUNX1 and TLE3 by mis-expressed FOXC1 blocks differentiation in acute myeloid leukemia. In Press Cell Reports
3. Shen-Hsi Yang, Munazah Andrabi, Rebecca Biss, Syed Murtuza Baker, Mudassar Iqbal, Andrew D. Sharrocks, ZIC3 Controls the Transition from Naive to Primed Pluripotency, Cell Reports, Volume 27, Issue 11, 2019, Pages 3215-3227.e6
4. Syed Murtuza Baker, Connor Rogerson, Andrew Hayes, Andrew D Sharrocks, Magnus Rattray; “Classifying cells with Scasat, a single-cell ATAC-seq analysis tool”, Nucleic Acids Research, 2018, gky950
5. Daniel H Wiseman*, Syed M Baker*, Arundhati V Dongre, Kristian Gurashi, Joanna A Storer, Tim CP Somervaille, Kiran Batta, Chronic myelomonocytic leukaemia stem cell transcriptomes anticipate disease morphology and outcome, EBioMedicine, 2020, Volume 58, 102904, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2020.102904.
*joint fist author