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Proteomic and mass spectrometric analysis of disease progression in Acute Myeloid Leukaemia


Project Description

Acute myeloid leukaemia is a disease where unfortunately outcomes have improved little in the recent past and new approaches are required in treatment of the disease. One major issue is relapse after initial treatment. A greater ability to understand or predict relapse would be beneficial for the patient. We have previously employed proteomics in leukaemia research to identify features of chronic myeloid leukaemia stem cells that, when targeted, extinguish the leukaemic clone (presently used kinase inhibitors do not achieve this). This work proceeds to clinical trials. We now wish to use the same strategy to investigate biomarkers for and mechanisms of relapse in Acute Myeloid Leukaemia (AML). We will use proteomics to study AML cells and AML patient plasma to identify features that predict relapse. We will use established mass spectrometry and informatics procedures to achieve these aims within the Stoller Biomarker Discovery Centre (a £25 million research centre that has developed the largest clinical proteomics facility in the world). This includes the ability to create digitised proteomics maps of tissue material or plasma samples using a novel mass spectrometry approach called Data Independent Acquisition mass spectrometry. After acquiring these maps they can be interrogated to develop algorithms that indicate or predict how a patient will respond to therapy within a training set of samples. Thereafter we will move to validate the signals found using a distinct sample set, developing we hope a new approach to stratification for appropriate or effective treatment in AML.

Training/techniques to be provided:
We will give a training in sample preparation using standard experimental haematology techniques. We will aslo provide training in sample preparation for mass spectrometry and use of mass spectrometry. Furthermore data analysis processes for proteomic datasets will also be provided.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in analytical biochemistry or mass spectrometry are encouraged to apply.

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

Applications are invited from self-funded students. 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.

References

1. Pearson, S., Guo, B., Azadbakht, N., Brazzatti, J., Patassini, S., Mulero-Navarro, S., Flotho, C., Gelb, B. D., Whetton, A. D., Proteomic Analysis of an Induced Pluripotent Stem Cell Model Reveals Strategies to Treat Juvenile Myelomonocytic Leukemia. Journal of Proteome Research. 2019 Oct. doi: 10.1021/acs.jproteome.9b00495
2. Geary, B., Walker, M.J., Snow, J.T., Lee, D.C.H., Pernemalm, M., Maleki-Dizaji, S., Azadbakht, N., Apostolidou, S., Barnes, J., Krysiak, P., Shah, R., Booton, R., Dive, C., Crosbie, P.A., Whetton, A. D. Identification of a Biomarker Panel for Early Detection of Lung Cancer Patients. Journal of Proteome Research. Sep 2019; 18(9), pp.3369-3382. doi: 10.1021/acs.jproteome.9b00287
3. Alanazi, B., Munje, C.R., Rastogi, N., Williamson, A.J.K., Taylor, S., Hole, P.S., Hodges, M., Doyle, M., Baker, S., Gilkes, A.F., Knapper, S., Pierce, A., Whetton, A. D., Darley, R.L., Tonks, A. Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia. Leukemia. In Press
4. Abraham SA, Hopcroft LEM, Carrick E, Drotar M, Dunn K, Williamson AJK, Korfi K, Baquero P, Park LE, Scott MT, Pellicano F, Pierce A, Copland M, Nourse C, Grimmond SM, Vetrie D, Whetton AD and Holyoake TL (2016) Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells. Nature 2016 Jun 16;534 (7607):341-6. doi: 10.1038/nature18288

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