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Modification of T helper cell function by synthetic biology approaches

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  • Full or part time
    Dr Daniel Hebenstreit
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Synthetic biology holds great promise for many diverse fields, including energy and food production and the enhancement of human health [1]. A particular aim of synthetic biology is it to modify functions of immune cells to control immune responses in a specific way. Recent efforts targeting T helper cells (CD4+) have been highly successful and have produced cells that resist HIV infection [2] or cells that could be controlled with regards to their proliferative properties [3]. Such accomplishments have a great potential for the treatment of many different diseases.

In this project, we are aiming to introduce more complex synthetic circuits into murine T helper cells in order to allow for a more precise and intricate control of their function. We will use genome editing in order to rewire signaling pathways associated with activation, cell division, growth rate, and cytokine secretion. This will yield cells that can be artificially instructed to fulfill a spectrum of diverse roles.

The project will initially involve transfections of murine cell lines to ectopically express factors and explore their suitability for our project. The results will be evaluated using a combination of single-molecule RNA-FISH [4], flow cytometry, and next generation sequencing. In later project stages, CRISPR/Cas9 technology [5] will be employed to re-engineer the cell lines to yield stable systems with controllable synthetic components.



Keywords: Immunology, synthetic biology, systems biology, gene expression, transcription, stochastic kinetics, biological noise, genome editing, mammalian cells

References


1. Lienert, F., et al., Nat Rev Mol Cell Biol, 2014. 15(2): p. 95.
2. Tebas, P., et al., N Engl J Med, 2014. 370(10): p. 901.
3. Chen, Y.Y., et al., Proc Natl Acad Sci U S A, 2010. 107(19): p. 8531.
4. Raj, A., et al., Nat Methods, 2008. 5(10): p. 877.
5. Ran, F.A., et al., Nat Protoc, 2013. 8(11): p. 2281.

How good is research at University of Warwick in Agriculture, Veterinary and Food Science?

FTE Category A staff submitted: 12.60

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