Download Transcriptional noise in CD4+ cells

Principal Supervisor name and department: Dr Daniel Hebenstreit, School of Life Sciences
Second Supervisor name and department: Barbel Finkenstadt, Statistics
Where will the student be based? School of Life Sciences, Warwick
PhD project title: Transcriptional noise in CD4+ cells
Project description:
The numbers of mRNAs and proteins that are found in a cell are usually low, amounting to less than
one hundred for most types of mRNA. The statistical distributions of these among the cells of an
otherwise identical population feature high variances. Yet, cells function reliably. It is thus a highly
interesting question how this expression ‘noise’ is transmitted through, and controlled by, the
complex network that is formed by the genes regulating each other. The system of mammalian CD4+
T cells represents a well-suited model to explore this question. Upon differentiation, CD4+ cells
orchestrate adaptive immune responses. The precise immune regulation exerted by these cell types
contrasts with the high variabilities that are seen for gene and protein expression levels. Based on a
combined experimental and theoretical approach, the aim of the project will be to study how
requirements for noise control have shaped the Th cell gene regulatory network topology and vice
versa. This will advance the understanding of CD4+ T cell biology and will reveal general features of
noise propagation and gene regulation in mammalian cells.
Key experimental skills involved:
 Basic cell and molecular biology
 Cell culture
 Flow Cytometry
 Possibly next generation sequencing
References:
1. Hebenstreit, D.; Deonarine, A.; Babu, M.M.; Teichmann, S.A., Duel of the fates: The role of
transcriptional circuits and noise in cd4+ cells. Curr Opin Cell Biol 2012, 24, 350-358.
2. Hebenstreit, D.; Fang, M.; Gu, M.; Charoensawan, V.; van Oudenaarden, A.; Teichmann, S.A., Rna
sequencing reveals two major classes of gene expression levels in metazoan cells. Mol Syst Biol
2011, 7, 497.
3. Munsky, B.; Neuert, G.; van Oudenaarden, A., Using gene expression noise to understand gene
regulation. Science 2012, 336, 183-187.
Contact details for application enquiries:
Daniel Hebenstreit
Assistant Professor
School of Life Sciences
University of Warwick
Gibbet Hill Campus
Coventry CV4 7AL, UK
Phone: +44 (0)24 76 574457
E-mail: [email protected]
Keywords: CD4, T cells, noise, gene expression, transcriptional regulation