Don't miss our weekly PhD newsletter | Sign up now Don't miss our weekly PhD newsletter | Sign up now

  Lightsheet microscopy to uncover the architecture of gene regulation in human cells and its role in cancer


   Faculty of Medical Sciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr Adam Wollman, Dr Aakash Basu, Prof J Higgins  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

All the information to make every cell in the human body is encoded in the same 3 billion DNA letters of genetic code. So what allows each cell to be so different and make up all the tissues and organs in the human body? Cells use regulating proteins called transcription factors (TF) to switch on and off genes at different times and places in the body, creating a myriad of different cell types with different functions. When this goes wrong, it can lead to diseases such as cancer.

To work, TFs have to find the correct few letters of DNA in the right gene among the billions in the genome. How they do this is not fully understood. Using advanced microscopes, which can image individual TF molecules inside living cells, We showed that TFs find their binding sites by clustering together, allowing them to search more quickly by binding to multiple strands of DNA simultaneously. At the same time exciting new techniques are being developed which go beyond looking only at the sequence of DNA – A,T,C,G – but its 3D shape and mechanical properties, like flexibility. These techniques are opening up a whole new way to study how genes are switched on and off. This project will combine both techniques to try to understand how TF clusters alter the shape and flexibility of DNA and vice versa and what might go wrong in diseases such as cancer.

This project will provide experience and extensive training in single-molecule and super-resolution microscopy, genomic technologies, optics, image analysis and programming. 

HOW TO APPLY

Applications should be made by emailing [Email Address Removed] with:

·        a CV (including contact details of at least two academic (or other relevant) referees);

·        a covering letter – clearly stating your first choice project, and optionally 2nd ranked project, as well as including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project(s) and at the selected University;

·        copies of your relevant undergraduate degree transcripts and certificates;

·        a copy of your IELTS or TOEFL English language certificate (where required);

·        a copy of your passport (photo page).

A GUIDE TO THE FORMAT REQUIRED FOR THE APPLICATION DOCUMENTS IS AVAILABLE AT https://www.nld-dtp.org.uk/how-apply. Applications not meeting these criteria may be rejected.

In addition to the above items, please email a completed copy of the Additional Details Form (as a Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.

Informal enquiries may be made to [Email Address Removed]

The deadline for all applications is 12noon on Monday 9th January 2023. 

Biological Sciences (4) Physics (29)

Funding Notes

Studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

Transcription factor clusters regulate genes in eukaryotic cells. (2017) eLife Aug;6 e27451.
Towards mapping the 3D genome through high speed single-molecule tracking of functional transcription factors in single living cells. (2019) Methods. 10.1016/j.ymeth.2019.06.021
Measuring DNA mechanics on the genome scale (2021) Nature. 10.1038/s41586-020-03052-3
Searching for sequence features that control DNA flexibility (2022). Biophysical Journal. 10.1016/j.bpj.2021.11.554
CDK1-mediated phosphorylation at H2B serine 6 is required for mitotic chromosome segregation (2019). Journal of Cell Biology.
Search Suggestions
Search suggestions

Based on your current searches we recommend the following search filters.