Kinetic efficiencies of DNA searching by disordered transcription factors
Lead Research Organisation:
University of Oxford
Department Name: Interdisciplinary Bioscience DTP
Abstract
Gene regulation is a fundamental process within cells and has roles in normal cell maintenance as well as disease. Transcription factors are the proteins responsible for this regulation and have been shown be disordered in structure i.e. not having a regularly defined structure. It is believed that this disorder plays a functional role. One potential role is in facilitating the binding during target DNA search within cells. This project will aim to characterise the disorder in a DNA-binding domain and examine its role in DNA sliding by using interactions with a random DNA sequence as a model.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011224/1 | 01/10/2015 | 31/03/2024 | |||
| 1757830 | Studentship | BB/M011224/1 | 01/10/2016 | 31/03/2021 |
| Description | Biochemical Society General Travel Grant |
| Amount | £414 (GBP) |
| Organisation | Biochemical Society |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2019 |
| End | 08/2019 |
| Description | Euromar Student Stipend |
| Amount | € 300 (EUR) |
| Organisation | EUROMAR |
| Sector | Charity/Non Profit |
| Country | France |
| Start | 08/2019 |
| End | 08/2019 |
| Description | Molecular simulations of disordered proteins |
| Organisation | Washington University in St Louis |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Within my project, I have described various transcription factor/DNA complexes using NMR, which is one of the first descriptions of a target search mode of a transcription factor. This includes chemical shift information for the protein backbone atoms. I will be providing these to Rohit Pappu's research group where they are interested in using NMR data to inform molecular dynamics simulations. |
| Collaborator Contribution | The collaboration is still in the early stages, so no contributions have been made so far except for the initial discussions that show our data and how the collaborators intend on proceding. |
| Impact | The collaboration is in the very early stages, where initial discussions have taken place and now the collaborators are starting to build the simulations. We will then send the NMR data that they require at the stage when they need it. |
| Start Year | 2020 |
| Description | A talk or poster - EuroIsmar 2019 Presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | EuroImsar in 2019 was a joint meeting, which takes place every two years, between the American NMR conference (Ismar) and the european counterpart (Euromar), which was held in Berlin. This was an international meeting of the leaders in magnetic resonance spectroscopy, including ESR and NMR. At the Gordon IDP conference in 2018, I was present at talks from several group leaders who also contributed talks at this conference, therefore I was familar with who they were. My talk was twenty minutes long, with 10 minutes for questions, within a session themed on analysis of biological systems using NMR. The audience for the talk was around 50-100, held within 4 paralell sessions. My talk was well received by the leading NMR experts on disordered proteins, with a few of these interested in me for future career prospects. |
| Year(s) Of Engagement Activity | 2019 |
| Description | A talk or poster - Interdisciplnary Bioscience DTP Annual Symposium Poster Presentation |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | The cohort that was current as of 2019 of the BBSRC Interdisciplinary Bioscience DTP and their supervisors were invited to this event. Prospective DTP students are also invited, who were current undergraduates at the local and national instiutions. I gave a poster presentation, which was the most up to date version of my project with regards to the highest impact results. Several people were interested in my poster, and this raised some interesting questions and discussions from those individuals. The purpose of the event is to enable me to have practice at delivering a poster presentation, and to also promote my research within the DTP and anybody else who attended the event. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Biochemistry Department Undergraduate Open Day |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Due to my project being heavily involved with NMR, I was asked to help work on the NMR stall during the Undergraduate Open day events. I was able to explain NMR and it uses for projects in Biochemistry, as well as show the prospective students my own project as an example. Several students were interested in what you can achieve by NMR, as a scale model of the 950 MHz spectrometer that Oxford has was shown during the demonstration. This sparked discussions with the parents of the students as well. Around 30 people talked to us personally, but around 300 people had actually seen the stand with my NMR data on show as well. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Poster presentation at Intrinsically Disordered Proteins Gordon Research Conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Other audiences |
| Results and Impact | Poster presentation entitled: Binding of the disordered basic region of CREB to DNA. This was to publicise our work and contribute towards the international conference. This work was also a significant part of my supervisors presentation during the conference as well. From what I have been told, the work was well received as it provides evidence towards a theory on how disordered proteins interact with DNA. |
| Year(s) Of Engagement Activity | 2018 |