Action! Modelling DNA nano-machines for deciphering their molecular mechanisms
Lead Research Organisation:
University of York
Department Name: Physics
Abstract
This computational PhD project aims to model experimental high-resolution structural snapshots of essential viral DNA nanomachines, including helicases and DNA packaging motors for unravelling how they work. The research will address the knowledge gap in the molecular mechanisms of several selected protein-nucleic acid machines, for which accurate X-ray structures have already been obtained in Antson lab (YSBL, Chemistry Department). One such machine is the papillomavirus E1 helicase, which unwinds dsDNA during viral replication. Another machine, targeted in this project, is the DNA packaging motor present in tailed bacteriophages and evolutionarily related herpes viruses (such as Cytomegalovirus). The machine translocates viral DNA, replicated within the host cell, into an empty pre-formed viral capsid. In spite of detailed structural information, it is still unknown how exactly these machines work.
The molecular motors will be simulated using the AMBER (Assisted Model Building with Energy Refinement) software, a molecular dynamics software package that simulates biomolecules through the use of the AMBER force fields. It therefore can show how the molecules move and flex, greatly increasing our understanding of the motor as currently only static pictures of it have been obtained.
The molecular motors will be simulated using the AMBER (Assisted Model Building with Energy Refinement) software, a molecular dynamics software package that simulates biomolecules through the use of the AMBER force fields. It therefore can show how the molecules move and flex, greatly increasing our understanding of the motor as currently only static pictures of it have been obtained.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509802/1 | 01/10/2016 | 31/03/2022 | |||
| 1950230 | Studentship | EP/N509802/1 | 01/10/2017 | 31/03/2021 | Antoinette Alevropoulos-Borrill |
| Description | The E1 helicase is a key nanomachine in the replication of DNA, which acts like a zip, separating the two strands of DNA. My studentship discovered a key component in understanding how it works. We found that the large chamber inside the E1 helicase has a very important function. When DNA passes through the helicase, this chamber allows the separation of the two strands of DNA, by providing the necessary space for the DNA to move and change shape. This in critical for DNA strand separation. |
| Exploitation Route | As we now understand how a key part of this helicase works, further work can use this knowledge to create effective antivirals. The E1 helicase is very important in the life-cycle of HPV and BPV, and creating drugs to target the E1 helicase could bring about a cure for this disease. On top of this, new projects could use our method to expand our understanding of other similar helicases. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Festival of Ideas - Family Fun Afternoon |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Around 200 children and 150 adults attended my DNA Detectives (2019) and DNA Bracelets (2018) stand where children could make bracelets with the genetic sequence of different organisms, as well as do DNA origami and Decode DNA crosswords. It taught both adults and children about DNA and genetics, and sparked an interest in science, with one parent reporting that his child had taken their DNA bracelet into school for "show and tell". Several adults also reported that they understood DNA better because of it and wanted to teach their children more about it. |
| Year(s) Of Engagement Activity | 2018,2019 |
| URL | http://agnesnoylab.wordpress.com |
| Description | Institute of Physics 2nd Physics Education for the 21st Century meeting "Making the Invisible Visible: Enhancing Learning Through Visualisation" |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I presented a 15 minute talk about how secondary school teachers, and lecturers at university, could use molecular simulations as a tool for teaching physics to their students. There was good engagement with the audience, with members taking note of the method to potentially use at their institution. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.iopconferences.org/iop/frontend/reg/tOtherPage.csp?pageID=835119&eventID=1340 |
| Description | Pint of Science - Event Organiser |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Over 40 members of the public attended a public lecture series across 3 days, which sparked questions and discussions and gave the audience a better understanding of a variety of different scientific research. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://pintofscience.co.uk/event/the-science-of-music-and-light |
| Description | University of York Headstart Iniative |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Over 30 students attended the University of York for a week-long program of talks, tours and activities to encourage them to go to University and do a STEM degree. |
| Year(s) Of Engagement Activity | 2019 |
| Description | University of York Isaac Physics Programme for Year 10 girls |
| Form Of Engagement Activity | Participation in an open day or visit at my research institution |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Schools |
| Results and Impact | Around twenty year 10 girls from the region participated in activities at the University of York including lectures, tours, problem solving sessions and online tutorials. It provided the students with greater confidence and aimed to encourage them to attend University, taking a STEM course. |
| Year(s) Of Engagement Activity | 2018,2019 |
| Description | Work Experience Week |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Presented two introductory presentations about molecular dynamics simulations and DNA super-coiling to a group of students, which promoted them to learn more about the subject. They presented this information to members of the Physics Department, where they demonstrated increased knowledge of biophysics applications, and greater interest in biophysics. |
| Year(s) Of Engagement Activity | 2019 |
| Description | YorNight - Meet your Molecules and Swimming Off the Wall |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | Over 1000 people attended our stall; Meet your Molecules and Swimming Off The Wall at YorNight. Meet your Molecules was an immersive virtual reality experience where people could walk around and move DNA binding proteins. Swimming Off The Wall showed a projection of swimming algae along with 3D images of carnivorous plants. The general public got a better understanding of DNA and genetics and it hopefully instead more children to engage with science. |
| Year(s) Of Engagement Activity | 2019 |
| URL | http://agnesnoylab.wordpress.com |