Principal Supervisor name and department: Dr Daniel Hebenstreit, School of Life Sciences
Where will the student be based? School of Life Sciences, Warwick
PhD project title:
Synthetic biology: designing reliable and predictable gene circuits in mammalian cells
Project description:
Synthetic biology holds great promise for many diverse fields, including energy and food production
and the enhancement of human health. A major aim of synthetic biology is it to construct artificial
gene circuits that function reliably and that can be tailored to different applications. Currently this is
not possible due to fluctuations and random variations on the molecular level. Systems based on
more than four or five regulatory interactions usually become unpredictable.
In this project, we will use genome editing in order to rewire signaling pathways in a mammalian cell
line. We will restrict variations in the general states of the cells [1, 2] in order to design more
complex synthetic gene circuits that are robust and predictable.
The project will initially involve transient transfections of the HEK293 cell line to ectopically express
factors and explore their suitability for our project. The results will be evaluated using a combination
of single-molecule RNA-FISH [3], flow cytometry, and next generation sequencing. In later project
stages, CRISPR/Cas9 technology [4] will be employed to re-engineer the cell lines to yield stable
systems with controllable synthetic components.
References:
1. Paulsson, J., Physics of Life Reviews, 2005. 2(2): p. 157-175. 2. Swain, P.S., M.B. Elowitz, and E.D. Siggia, Proc Natl Acad Sci U S A, 2002. 99(20): p. 12795800. 3. Raj, A., et al., Nat Methods, 2008. 5(10): p. 877-9. 4. Ran, F.A., et al., Nat Protoc, 2013. 8(11): p. 2281-308. 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: d.hebenstreit@warwick.ac.uk
Keywords:
Synthetic biology, systems biology, gene expression, transcription, stochastic kinetics, biological
noise, genome editing, mammalian cells