Viral manipulation of intracellular signalling pathways dictate cell fate and haematopoiesis

Matthew Reeves (primary)
Infection
UCL
Radu Zabet (secondary)
Blizzard Institute
QMUL

Abstract

Haemtopoietic cell differentiation is a complex process that is dictated by specific patterns of gene expression, 3D DNA architecture and epigenetic landscape acting in response to signalling cues. Human cytomegalovirus (HCMV) is a herpesvirus that establishes lifelong latent infections in the haematopoietic cell compartment. Recent evidence indicates that HCMV ‘reprogrammes’ infected CD34+ cells committing them myelo-monocytic fate during differentiation which we hypothesise is via manipulation of intracellular signalling and subsequent consequences for downstream gene expression. Our vision is to use the virus as a molecular tool to identify fundamental signalling events that underpin changes important for cell fate.


References

Reeves M.B. (2020) Cell signalling and cytomegalovirus reactivation: what do src family kinases have to do with it? Biochem. Soc. Trans. 48(2): 667-75
Reeves M.B. (2018) Viral programming of progenitor cell commitment Nat. Micro.4: 398-99
Dupont L. & Reeves M. (2016) Cytomegalovirus latency and reactivation: Recent insights into an age old problem. Rev. Med. Virol. 26(2): 75-89
Chathoth, K. T. & Zabet, N. R. Chromatin architecture reorganisation during neuronal cell differentiation in Drosophila genome. Genome Res. 29, 613–625 (2019).
Martin, P. C. N. & Zabet, N. R. Dissecting the binding mechanisms of transcription factors to DNA using a statistical thermodynamics framework. , Computational and Structural Biotechnology Journal, 18: 3590-3605.


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyMicrobiology
Techniques & Approaches
BioinformaticsGeneticsMathematics / StatisticsMolecular Biology