Transcription is the process in the cell where the genetic code from DNA is copied into mRNA by the molecular motor RNA polymerase (RNAP) as it translocates along the DNA. Since the DNA is helical there is relative rotation to the RNAP which leads to local DNA supercoiling which can enhance or suppress the action of RNAP, affecting its ability to copy the gene in question and therefore is a fundamental physical mechanism that influences gene expression. Recent discoveries increasingly show that many genes are co-located in compressed formats, being either convergent, divergent, aligned or nested [1].
This project will use artificially constructed compressed gene templates both in vivo and in vitro to understand how these genetic structures relate to expression efficiency. Gene expression from bacterial plasmids with convergent and divergent promoters will be determined and compared with mechanistic in vitro studies on similar constructs using high resolution imaging of individual molecular complexes using atomic force microscopy (AFM) [2,3]. The translocation of DNA through RNAP as transcription occurs in vitro was first followed using atomic force microscopy (AFM) at the single molecule level [4] and more recently, we have been investigating the interactions of more than one RNAP on a single DNA template [5,6].
There is a nested gene system involved in tooth enamel development where the expression of the biomineralising amelogenin protein may be compromised. The outcomes of this project will better inform us about such fundamental aspects of developmental biology and diseased states associated with altered gene expression.
Aims & Objectives:
- Construction of DNA plasmids for model expression in bacterial cultures
- Construction of DNA gene models for AFM imaging based on established convergent and tandem systems.
- Ex-situ AFM imaging of transcriptional outcomes on gene model templates.
- Correlation of AFM RNAP positional data with bacterial expression data.
- In-situ High-speed AFM direct imaging of multi-RNAP transcription.
- Development of DNA origami nanostructures for AFM in-situ imaging of transcription events.
You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject. This project would suit a student with a background in physical science with interest in biological systems, or in biological science with an interest in physical techniques. Experience could include but is not limited to physics, biophysics, chemistry, biochemistry, chemical engineering etc..
The Faculty of Medicine and Health minimum requirements are:
- British Council IELTS - score of 6.5 overall, with no element less than 6.0
- TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.
How to apply:
To apply for this scholarship applicants should complete an online Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School [Email Address Removed]
We also require 2 academic references to support your application. Please ask your referees to complete the online Scholarship Reference form on your behalf and send directly to [Email Address Removed] by no later than Friday 9 April 2021.
If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead you should email [Email Address Removed] to inform us you would like to be considered for this scholarship project.
Any queries regarding the application process should be directed to [Email Address Removed]
Closing date for this scholarship is Friday 9 April 2021.
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