The characterisation of bacterial nucleoside diphosphate kinase (NDK) proteins and their effects on haemopoeitic stem cells

Köpf, Monika (2014). The characterisation of bacterial nucleoside diphosphate kinase (NDK) proteins and their effects on haemopoeitic stem cells. University of Birmingham. M.Res.

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Abstract

Introduction: Nucleoside Diphosphate Kinases (NDK) are a family of small conserved proteins present in all cells. They are involved in the synthesis of nucleoside triphosphates (NTP) and nucleoside diphosphates (NDP) which maintain nucleotide pools in the cell. NDK play an important role in the cells metabolic processes. Most NDK proteins are known to form hexameric quaternary structure. Hypothesis: This study tested the hypothesis that bacterial NDK proteins can promote the survival of haemopoietic stem cells. Infection has been identified as a risk factor for progression to AML in patients with pre-leukaemic conditions. Methods: The over expression of bacterial NDK from four bacterial species; Escherichia coli, Klebsiella pneumonie, Staphylococcus aureus and Streptococcus pneumoniae, were cultured for 5 days with CD34-ve and CD34+ cells from umbilical cord bloods and leukaemic samples. The expression of NDK at mid-logarithmic and at stationary phase were analysed, and NDK knockout mutants and site directed mutants were produced from conserved domains of the NDK, to characterise important domains which could play a role in the NDK survival mechanism on haemopoietic stem cells. Results: Preliminary results have suggested that bacterial NDK proteins may increase the survival of haemopoietic stem cells, however further work is needed to confirm such findings. The NDK mutants have shown to have a disrupted biology which leads to an altered expression in NDK. The Mutant 3, a disruption in the KPN loop, has shown a disruption in the structure of NDK. Conclusion: The results suggest that bacterial NDK proteins could play a role in promoting the survival of leukaemic stem cells. This would impact patient care and treatment as well as requiring ongoing medical research into bacterial NDK proteins; and their interactions with leukaemic stem cells. The increased risk of neutropenic infections in patients undergoing chemotherapy could have a greater link to leukaemia than first thought and NDK proteins may have a role in bacterial pathogenicity by disrupting haemopoiesis.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

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