Investigating the stability and function of i-motif DNA

Lead Research Organisation: University of East Anglia
Department Name: Pharmacy

Abstract

It is assumed that DNA exists as a double helix, the structure first described by Watson and Crick in 1953. However, it is lesser-known that DNA can adopt many different types of structure. DNA is composed of four different "building blocks" called bases: adenine, guanine, thymine and cytosine. DNA sequences rich in cytosine can form alternative secondary structures called i-motifs, first discovered in 1993. Sequences of this type are widespread throughout our genome and may play a role in gene expression, but there are many fundamental questions unanswered. The stability of i-motif structures is highly dependent on the particular sequence of bases. To understand which sequences are more likely to form i-motifs in biology, an understanding of their stability is required. This project proposes a systematic investigation of a library of different DNA sequences to determine the optimum sequence requirements for stable i-motif formation. This will allow us to define rules to predict the stability of i-motif structure based on the type of DNA sequence. We will then use this information for computational analysis of the human genome to estimate the number of sequences which could potentially form i-motif structures, and where these reside in the human genome. Using a mixture of molecular biology techniques, we will investigate the impact of stabilisation of i-motif structure on transcription and de-convolute the interplay between the dynamics of i-motifs and G-quadruplexes (structures which have previously been well-characterised) on gene expression. This proposal will reveal which i-motif sequences are most stable and potentially new targets for drug design, therapeutics and structural investigation.

Technical Summary

This proposal is about the investigation of the stability and potential biological functions of i-motif DNA secondary structures. The project will use a range of biophysical and molecular biological techniques to answer the following key questions:
1) Which types of DNA sequences form the most stable i-motif structures?
2) How does epigenetic modification change the stability and dynamics of these structures?
3) Can targeting i-motifs with small molecule ligands interfere with gene expression?
4) Is there any interplay between the position of i-motif and G-quadruplex structures and the effects on gene expression and are there any synergistic effects between them?
Biophysical analysis will be performed on C-rich DNA libraries. UV melting and annealing experiments will be used to determine the thermal stability of the structures and insight into the kinetics of folding/unfolding processes. UV thermal difference spectroscopy will provide indicative spectra to characterise the type of DNA secondary structure formed. CD spectroscopy will provide further insight on the type of secondary structure in solution and will be used to determine the transitional pH of the sequence to give an indication of the pH dependent stability of the structure. Footprinting will be used to give insight into folding and topology. In vitro analysis will be performed using an RNA polymerase stop assay to indicate whether DNA secondary structures disrupt transcription. In vivo methodology will include cloning of plasmids for a luciferase based reporter gene assay for assessment of the effect of DNA secondary structure on transcription. Further experiments will utilise quantitative real time PCR, which measures the quantity of mRNA produced from chromosomal DNA. Both in vitro and in vivo experiments will be investigated using previously characterised i-motif and G-quadruplex interacting ligands as chemical tools.

Planned Impact

The findings from this study will develop an understanding of the stability of different types of DNA sequences which are able to form i-motif secondary structures and also their potential effects in biology. The work will directly impact the post-doctoral research assistant working on the project, who will be trained in both biophysical and bioinformatic techniques. This will contribute towards not only their education and professional development but also the education economy for UEA, Norwich Research Park, East Anglia and the UK.

The identification of regions in the human genome where the most stable i-motif forming sequences are present will identify novel targets for further structural investigation and targets for drug design. This will directly affect interest in the design of small molecule ligands to interact with i-motif DNA. The number of stable potential i-motif forming sequences in the human genome is expected to be much lower compared to other types of secondary structures such as G-quadruplexes; this will allow higher chances of achieving high specificity. The work will indicate whether it is possible to affect transcription by targeting i-motif DNA. From this, work can be built on the potential of small molecule ligands to stabilise or destabilise i-motif structures for use as nanotechnological and chemical biological tools, or in the development of therapeutics for genetic disease. In this aspect, industry would benefit, for example, pharmaceutical companies involved in transcriptional-related drug discovery. This will also impact the applicant's research projects involving design and development of small molecules to target i-motif DNA, and consequently will aid applications for financial support for these studies.

The outcomes of this work will increase the opportunity for development of further national and international collaborations. For example, there are a large number of world-leading researchers who are working on DNA secondary structure and the results from the work in this proposal would inspire many of these researchers to consider working on the i-motif forming sequence in their DNA or gene of interest. This work would have the opportunity to impact a very board range of researchers, from those working on i-motif and/or G-quadruplexes, DNA based nanotechnology, genome bioinformatics, gene expression and epigenetics (hence also the pharmaceutical industry) to those interested in DNA-based self assembly and nanotechnology (and therefore the material sciences and photonics industry).

Finally, the general public would benefit from this work as it signifies hope for further understanding of how genes are read and potential novel targets for therapeutics for genetic diseases. Consequently, we would expect that there will be a wide range of beneficiaries: academic scientists, industrial enterprise (from pharmaceuticals to nanotechnology) and the general public.

Publications

10 25 50
 
Description We have discovered that copper cations can re-fold DNA from one form to another. We have shown that an known drug, called mitoxantrone, can bind and stabilise i-motif DNA. We have found multiple examples of i-motifs which are stable under neutral conditions - implicating i-motifs in biology. We have developed a way to screen compounds for i-motif. We have found that epigenetic alteration of DNA affects stability of i-motif structure and also where in the sequence this has the largest impact and how this relates to the actual position where these occur in the genome. We have found compounds which were formally thought to be specific for G-quadruplex bind i-motif. We have compounds which stabilise i-motif and alter gene expression.
Exploitation Route Use of the new conditions for changing DNA structure may be used in nanotechnology. Mitoxantrone is commercially available and can be used as a compound in future i-motif studies. Others can use the i-motif forming sequences which we have identified which are stable at neutral pH to study in biology. People can use our new screen for finding i-motif ligands, or use the ones we have found in their studies. The work on epigenetics will be useful for researchers interested in how genes are expressed and altered.
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description A press release on the findings from our i-motif-hairpin transition has shown wide interest in this type of work from the general public and general science interest.
First Year Of Impact 2015
Sector Digital/Communication/Information Technologies (including Software),Education
Impact Types Cultural,Societal

 
Description Horizon 2020
Amount £58,088 (GBP)
Organisation European Union 
Sector Public
Country European Union (EU)
Start 01/2016 
End 12/2018
 
Description Pathfinder Awards
Amount £100,406 (GBP)
Funding ID 204515/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2017 
End 05/2018
 
Description UK-US platform for the study of RNA structure in living cells
Amount £49,395 (GBP)
Funding ID BB/N022572/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2016 
End 04/2020
 
Description Andy Gates 
Organisation University of East Anglia
Department School of Biological Sciences UEA
Country United Kingdom 
Sector Academic/University 
PI Contribution Aiding characterisation of DNA structures Applied for funding from the Royal Society
Collaborator Contribution Investigating DNA structures in bacteria Expertise in Kinetics
Impact Royal Society funding Reversible DNA i-motif to hairpin switching induced by copper(II) cations paper
Start Year 2010
 
Description Antonio Randazzo 
Organisation University of Naples
Country Italy 
Sector Academic/University 
PI Contribution We have found G-quadruplex ligands which also bind i-motif. The Randazzo group have also found similar results. We decided to join forces with this work. We have contributed SPR and FID biophysical experiments.
Collaborator Contribution The Randazzo group have done FRET, NMR and CD.
Impact We are preparing a publication
Start Year 2017
 
Description Benjamin Bax 
Organisation University of York
Country United Kingdom 
Sector Academic/University 
PI Contribution Bax and co-workers have successfully applied for funding from Diamond where I am a team member
Collaborator Contribution Applied for funding from Diamond (XChem)
Impact Successful funding bid.
Start Year 2017
 
Description Chris Morris 
Organisation University of East Anglia
Department School of Pharmacy
Country United Kingdom 
Sector Academic/University 
PI Contribution Morris and I share a PhD student funded by the BBSRC DTP
Collaborator Contribution Morris and I share a PhD student funded by the BBSRC DTP
Impact Morris and I share a PhD student funded by the BBSRC DTP October 2017-September 2021. We have also applied for funding from Diabetes UK
Start Year 2017
 
Description Laszlo Fabian 
Organisation University of East Anglia
Department School of Pharmacy
Country United Kingdom 
Sector Academic/University 
PI Contribution We have found copper (I) cations can help fold i-motif - used biophysical methods to show this
Collaborator Contribution Laszlo has provided computational studies to support our work
Impact We have a publication which is currently under revision
Start Year 2017
 
Description Lukas Trantirek 
Organisation Central European Institute of Technology (CEITEC)
Country Czech Republic 
Sector Charity/Non Profit 
PI Contribution We have found ligands which bind i-motif.
Collaborator Contribution Lukas has hosted one of my PhD students for a week to perform NMR experiments. This was funded by an iNEXT grant
Impact None yet
Start Year 2017
 
Description Nicole Smith 
Organisation University of Western Australia
Department School of Molecular Sciences
Country Australia 
Sector Academic/University 
PI Contribution We have connected with the Smith group and joined forces looking at the epigenetics of i-motif
Collaborator Contribution Nicole's group have looked at bisulphite sequencing data to determine for two different cell types exactly where i-motif forming sequences get methylated.
Impact We are currently preparing a publication together
Start Year 2017
 
Description Nicole Smith 
Organisation University of Western Australia
Department School of Molecular Sciences
Country Australia 
Sector Academic/University 
PI Contribution We have connected with the Smith group and joined forces looking at the epigenetics of i-motif
Collaborator Contribution Nicole's group have looked at bisulphite sequencing data to determine for two different cell types exactly where i-motif forming sequences get methylated.
Impact We are currently preparing a publication together
Start Year 2017
 
Description Steven Smith 
Organisation City of Hope National Medical Center
Country United States 
Sector Charity/Non Profit 
PI Contribution We have applied for NIH funding to support on-going work involving looking at the effects of epigenetic changes to DNA on I-motif structure. We will be analysing sequences synthesised by Steven's lab.
Collaborator Contribution Synthesis of the sequences required with epigenetic modifications within. Steven is PI on the NIH grant which was submitted late 2015. Steve's group have found sequences which are mutated in cancer which would result in i-motif structures not forming.
Impact Biochemistry https://pubs.acs.org/doi/abs/10.1021/acs.biochem.7b00628 we are also preparing another publication Multi-disciplinary (chemistry - biology)
Start Year 2015
 
Description Vaclav Brazda 
Organisation Academy of Sciences of the Czech Republic
Department Institute of Biophysics
Country Czech Republic 
Sector Public 
PI Contribution Vaclav sent a PDRA to work in my research group we trained them in certain techniques
Collaborator Contribution Vaclav sent their PDRA to work in my research group for 6 months
Impact We have written an application to Alzheimer's research UK
Start Year 2017
 
Description Yiliang Ding 
Organisation John Innes Centre
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Applied as Co-I and successfully received funding from the BBSRC for travel/exchange of staff between our labs and labs in the US. We have applied for a BBSRC responsive mode grant in the April 2017 round, which was unsuccessful (BBSRC References: BB/R008620/1 and BB/R009163/1). We are getting more preliminary data and will submit again in September.
Collaborator Contribution Ding is PI on the travel grant.
Impact Successful travel grant: BBSRC BB/N022572/1 Multi-disciplinary (chemistry - biology)
Start Year 2015
 
Description 2017 Invited research Seminar. CEITEC, Brno, Czech Republic 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Invited research Seminar. CEITEC, Brno, Czech Republic. Attended by approx. 100 postgraduate and undergraduate students. This resulted in development of collaborations with the Trantriek and Brazda groups, one visiting PDRA came for 6 months at the end of 2017.
Year(s) Of Engagement Activity 2017
 
Description 2017 Invited research seminar. Wymondham College, Wymondham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Approx. 60 6th form pupils attended an interactive teaching session about DNA structure and function and how our research fits in this. Multiple questions afterwards. One student asked to come and see the lab for a day shadowing, which we hosted a couple of months later.
Year(s) Of Engagement Activity 2017
 
Description 2017 Invited speaker. NSFC-RSC Symposium on Chemical Biology, London, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at a UK-China event organised by the RSC. Lots of questions at the end.
Year(s) Of Engagement Activity 2017
 
Description 2017 Invited speaker. Stephen Hawkings Society, St Albans, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Gave a talk on my research to school pupils to raise awareness of the science behind it but also develop interest in Science in general.
Year(s) Of Engagement Activity 2017
 
Description 2017 Selected talk. 6th Meeting on Quadruplex Nucleic Acids, Prague, Czech Republic 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Gave a talk at the 6th International Conference on Quadruplex Nucleic acids. The audience was approx. 300 people. Many questions and parise for our work afterwards. This resulted in collaborations between my group an the Randazzo group (Italy) and Trantriek group (Czech Republic).
Year(s) Of Engagement Activity 2017
 
Description 2017 Selected talk. Cambridge 7th Nucleic Acids Symposium, Cambridge, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a selected talk at the Cambridge 7th Nucleic Acids Symposium, Cambridge, UK. This resulted in lots of questions about our work. A collaboration with Benjamin Bax has been established and also invited to give a talk at a conference in Japan (FISNA) in 2018.
Year(s) Of Engagement Activity 2017
 
Description Advertising to teachers 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact As a STEM ambassador I have offered the opportunity to give talks/sessions within schools in Norfolk and Suffolk
Year(s) Of Engagement Activity 2016
URL http://www.connecteb.co.uk/new-activities-calendar/2016/11/24/dr-zoe-waller-stem-ambassador-activiti...
 
Description Balasubramanian group Reunion 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Balasubramanian group Reunion "Adventures with the other strand: targeting i-motif DNA" (Cambridge 2016)
Audience a mixture of people from industry, academia, general public (non-science), students etc.
Made connections with ex-group members to develop potential collaborations
Year(s) Of Engagement Activity 2016
 
Description Chem. Commun. 2016, 52, 13511-13514. (Explained on YouTube: https://www.youtube.com/watch?v=DNGRZd35ZTQ&t=182s) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A Youtube video aimed at a general audience. Control of bacterial nitrate assimilation by stabilisation of G-quadruplex DNA Z. A. E. Waller,* B. J. Pinchbeck, B. Seewoodharry Buguth, T. Meadows, D. J. Richardson, A. J. Gates*, Chem. Commun. 2016, 52, 13511-13514.
(Explained on YouTube: https://www.youtube.com/watch?v=DNGRZd35ZTQ&t=182s)
Year(s) Of Engagement Activity 2016
URL https://www.youtube.com/watch?v=DNGRZd35ZTQ&t=182s
 
Description Chem. Commun., 2015, 51, 14099-14102 (Explained on YouTube: https://www.youtube.com/watch?v=01bEnhtldzQ) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact 1. Reversible DNA i-motif to hairpin switching induced by copper(II) cations. H. A. Day, E. P. Wright, C. J. MacDonald, A. J. Gates and and Z. A. E. Waller,* Chem. Commun., 2015, 51, 14099-14102
(Explained on YouTube: https://www.youtube.com/watch?v=01bEnhtldzQ for a general audience
Year(s) Of Engagement Activity 2015
URL https://www.youtube.com/watch?v=01bEnhtldzQ
 
Description Chemistry and Pharmacy Summer School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Two day residential experience. As part of this my PDRA engaged with students by explaining about what we are working on to the year 12 students.
Year(s) Of Engagement Activity 2016
 
Description Cromer group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Explained about DNA structure, with reference to our work on I-motifs. Described what they are, related to how this is relevant to genetic disease. Held a very intense Q and A session after, with my PDRA. Very engaged audience!
Year(s) Of Engagement Activity 2016
 
Description Drug Discovery Roadshow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Talk at the Drug Discovery Roadshow: "Working in partnership to accelerate novel therapeutic development: A case study in nanotechnology and chemical biology" (CRUK Research Institute, Cambridge) 2016
Audience mix of charities, funders, industry and academics
Encouraged people to try novel ideas out. Many people spoke with me afterwards to state they were inspired by my story.
Year(s) Of Engagement Activity 2016
 
Description Explaining work at Wisbech Diabetes UK support group 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Gave a presentation about DNA and explained how our work can give a better understanding about DNA structure and the potential with genetic diseases such as Diabetes
Year(s) Of Engagement Activity 2015
 
Description Future Radio 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact I was interviewed on Future Radio about our work on i-motif and how we can use DNA for computing
Year(s) Of Engagement Activity 2015
 
Description Invited Chemistry Seminar. Sheffield University, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Gave a research seminar at Sheffield School of Chemistry. Lots of questions. Resulted in one student applying to do a BBSRC funded PhD in my group. I have a potential collaboration with Dr Tim Craggs which we are developing.
Year(s) Of Engagement Activity 2017
 
Description Invited research Seminar. Wymondham Diabetes UK group, Wymondham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact I gave a talk about our research to a Diabetes UK support group. There were approx. 50 attendees and they were engaged with questions about the work.
Year(s) Of Engagement Activity 2017
 
Description Invited research seminar, Department of Pharmacy, University of Naples, Italy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave a talk at the University of Naples about my research project. It resulted in deciding that we should collaborate on a particular aspect of the work. We are currently preparing a manuscript for publication
Year(s) Of Engagement Activity 2017
 
Description Ipswich Diabetes UK support group engagement 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Visited Diabetes UK support group in Ipswich - explained about DNA, our work on i-motifs, what we have found and the potential for learning more about diseases such as diabetes.
Year(s) Of Engagement Activity 2015,2016
URL http://ipswich.diabetesukgroup.org/events/group-public-launch-meeting
 
Description Nucleic Acids Res. 2017, 45, 2951-2959. (Explained on YouTube: https://www.youtube.com/watch?v=RlEnUctL07M&t=24s) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Youtube video for a general audience for Identification of multiple genomic DNA sequences which form i-motif structures at neutral pH. E. P. Wright, J. L. Huppert, Z. A. E. Waller* Nucleic Acids Res. 2017, 45, 2951-2959.
(Explained on YouTube: https://www.youtube.com/watch?v=RlEnUctL07M&t=24s)
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=RlEnUctL07M&t=24s
 
Description Pacifichem 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Talk at Pacifichem: "C-Quadruplex? Adventures with the "Other" Strand" (Hawaii, 2015 during maternity leave - PDRA gave the talk)
Year(s) Of Engagement Activity 2015
 
Description Press Release for Hairpin Work 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Interview about publication: Reversible DNA i-motif to hairpin switching induced by copper(II) cations
Radio Interview - BBC Norfolk
Radio Interview - Future Radio

Worldwide magazine coverage
The Sunday Business Post 20/08/2015, p.12
Oman Observer 20/08/2015
Med India 20/08/2015
Technology Networks 20/08/2015
The TeCake 21/08/2015
PC-Tablet India 21/08/2015
Datacentre Management 21/08/2015
Oman Observer 21/08/2015, p.11
Eastern Daily Press 22/08/2015, p.40

Several interviews for magazines
Year(s) Of Engagement Activity 2015
URL https://www.uea.ac.uk/about/-/how-uea-research-could-help-build-computers-from-dna
 
Description RSC Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Undergraduate students
Results and Impact RSC Lecture: "Think you know the structure of DNA?" (Bradford, 2016)
Year(s) Of Engagement Activity 2016
 
Description Radio Norfolk 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact I was interviewed on BBC Radio Norfolk about our work on i-motif and how we can use DNA for computing
Year(s) Of Engagement Activity 2015
 
Description Sci Reports. 2016, 6, 39456. (Explained on YouTube: https://www.youtube.com/watch?v=fA3gaP4SpW8) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact YouTube video for a general audience for Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences. E. P. Wright, H. A. Day, A. M. Ibrahim, J. Kumar, L. J. E. Boswell, C. Huguin, C. E. M. Stevenson, K. Pors,* Z. A. E. Waller* Sci Reports. 2016, 6, 39456.
(Explained on YouTube: https://www.youtube.com/watch?v=fA3gaP4SpW8)
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=fA3gaP4SpW8
 
Description Talk at Bath School of Pharmacy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talk at Bath School of Pharmacy "Stabilising the i-Motif with Cations and Ligands"
Audience of academics and research groups.
Potential collaborations with 2 new people.
Year(s) Of Engagement Activity 2016
 
Description Talk at Organic RSC Eastern meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talk at Organic RSC Eastern meeting: "Targeting i-Motif DNA with Small Molecule Ligands" (2016, during maternity leave KIT day)
Year(s) Of Engagement Activity 2016
 
Description Talk at the 5th International Meeting on Quadruplex Nucleic Acids 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact 5th International Meeting on Quadruplex Nucleic Acids: "Stabilising the i-Motif with Cations and Ligands" (Bordeaux, 2015)
Year(s) Of Engagement Activity 2015
 
Description The School of Pharmacy Annual Research Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talk at the School of Pharmacy Annual Research Day: "The Fantastic Four" (JIC, 2015)
Year(s) Of Engagement Activity 2015
 
Description Video describing "reversible DNA i-motif to hairpin switching induced by copper(II) cations" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is a short video describing my latest publication to a general audience.
Year(s) Of Engagement Activity 2015
URL https://youtu.be/01bEnhtldzQ
 
Description Video explaining "Control of bacterial nitrate assimilation by stabilization of G-quadruplex" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is a short video describing our latest publication to a general audience.
Year(s) Of Engagement Activity 2016
URL https://youtu.be/fA3gaP4SpW8
 
Description Video explaining "Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is a short video describing our latest publication to a general audience.
Year(s) Of Engagement Activity 2016
URL https://youtu.be/fA3gaP4SpW8
 
Description Video explaining "Multiple genomic DNA sequences which form i-motif structures at neutral pH" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact This is a short video describing our latest publication to a general audience.
Year(s) Of Engagement Activity 2017
URL https://youtu.be/RlEnUctL07M
 
Description YouTube to explain Biochemistry, 2017, 56, 4879-4883. (Explained on YouTube: https://www.youtube.com/watch?v=-9rMlbbo91s) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact YouTube video to explain to a general audience: Substitution of Cytosine with Guanylurea Decreases Stability of i-Motif DNA. E. P. Wright, K. Lamparska, S. S. Smith, Z. A. E. Waller* Biochemistry, 2017, 56, 4879-4883.
(Explained on YouTube: https://www.youtube.com/watch?v=-9rMlbbo91s)
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=-9rMlbbo91s
 
Description YouTube video to explain Org. Biomol. Chem. 2017, 15, 5669-5673. (Explained on YouTube: https://www.youtube.com/watch?v=sSmkHKTFaTc) 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact YouTube video to explain to a general audience... Identification of new DNA i-motif binding ligands through a fluorescent intercalator displacement assay Q Sheng, JC Neaverson, T Mahmoud, CEM Stevenson, SE Matthews, Z. A. E. Waller* Org. Biomol. Chem. 2017, 15, 5669-5673.
(Explained on YouTube: https://www.youtube.com/watch?v=sSmkHKTFaTc)
Year(s) Of Engagement Activity 2017
URL https://www.youtube.com/watch?v=sSmkHKTFaTc