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Combining single-molecule biophysics, DNA origami construction and low temperature plasmas to develop more efficient ways to kill harmful cells

Project Description

The DNA in a human cell is folded and compacted for storage by proteins and mechanisms that are incompletely understood; without these processes the DNA in one human cell would be around two metres in length. In vitro, we can fold smaller lengths of DNA into 2D or 3D DNA origami by careful design of specific binding sites. Plasma is an overall electrically neutral state of matter created by passing an electromagnetic field through a gas; it breaks bonds and forms positive, negative, and neutral species, along with photons. Low temperature plasma (LTP) is currently being developed as a novel prostate cancer treatment which acts to induce cell death in the tumour cells via DNA damage. LTP may provide considerable advantages over existing treatments for prostate cancer as plasma can be guided down a needle to allow treatment in the patient without highly invasive surgery. Key to killing harmful cells is to the ability to controllably induce DNA damage. However, existing methods to characterize the extent of DNA damage are relatively imprecise. This project will enable you to develop methods to controllably and precisely characterize the extent of DNA damage in a range of test DNA origami structures using LTPs.

Your project will allow you to:

1. Develop DNA origami structures. You will develop a range of DNA origami structures to act as biomimetic test structures for characterizing DNA damage.

2. Optimise LTP-mediated DNA damage. You will optimise and develop methods to induce controllable DNA damage in DNA origami samples, and correlate damage with measured plasma generated reactive species.

3. Characterise DNA damage. You will develop methods of single-molecule biophysics, including super-resolution fluorescence microscopy and atomic force microscopy, to precisely characterize the efficacy and mechanism of LTP-mediated DNA damage on DNA origami structures.

Funding Notes

The majority of decisions on funding for PhD positions will be made in March following interviews in February. Apply by 31 January 2019 to be considered for funding.

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