UK-US platform for the study of RNA structure in living cells

Lead Research Organisation: John Innes Centre
Department Name: Cell and Develop Biology

Abstract

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Description Dr. Zoe Waller and Dr. Yiliang Ding has successfully obtained a BBSRC grant working on aging and we are working on one manuscript regarding I-motif function in plants. We were submitting a NSF/BBSRC grant in Jan.
Exploitation Route Due to the maternal leave of Dr. Zoe Waller, We moved our in person workshop in May.
Sectors Agriculture, Food and Drink,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www.uea.ac.uk/pharmacy/news-and-events/-/asset_publisher/w7O8j7rUDTtg/blog/id/31426853
 
Description i-Motifs: Sequence, Structure and Function in Ageing
Amount £64,268 (GBP)
Funding ID BB/W000962/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2021 
End 12/2024
 
Title G4Atlas: a comprehensive transcriptome-wide G-quadruplex database 
Description RNA G-quadruplex (rG4) is a vital RNA tertiary structure motif that involves the base pairs on both Hoogsteen and Watson-Crick faces of guanines. rG4 is of great importance in the post-transcriptional regulation of gene expression. Experimental technologies have advanced to identify in vitro and in vivo rG4s across diverse transcriptomes. Building on these recent advances, here we present G4Atlas, the first transcriptome-wide G-quadruplex database, in which we have collated, classified, and visualized transcriptome rG4 experimental data, generated from rG4-seq, chemical profiling and ligand-binding methods. Our comprehensive database includes transcriptome-wide rG4s generated from 82 experimental treatments and 238 samples across ten species. In addition, we have also included RNA secondary structure prediction information across both experimentally identified and unidentified rG4s to enable users to display any potential competitive folding between rG4 and RNA secondary structures. As such, G4Atlas will enable users to explore the general functions of rG4s in diverse biological processes. In addition, G4Atlas lays the foundation for further data-driven deep learning algorithms to examine rG4 structural features. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact RNA G-quadruplex (rG4) is a vital RNA tertiary structure motif that involves the base pairs on both Hoogsteen and Watson-Crick faces of guanines. rG4 is of great importance in the post-transcriptional regulation of gene expression. Experimental technologies have advanced to identify in vitro and in vivo rG4s across diverse transcriptomes. Building on these recent advances, here we present G4Atlas, the first transcriptome-wide G-quadruplex database, in which we have collated, classified, and visualized transcriptome rG4 experimental data, generated from rG4-seq, chemical profiling and ligand-binding methods. Our comprehensive database includes transcriptome-wide rG4s generated from 82 experimental treatments and 238 samples across ten species. In addition, we have also included RNA secondary structure prediction information across both experimentally identified and unidentified rG4s to enable users to display any potential competitive folding between rG4 and RNA secondary structures. As such, G4Atlas will enable users to explore the general functions of rG4s in diverse biological processes. In addition, G4Atlas lays the foundation for further data-driven deep learning algorithms to examine rG4 structural features. 
URL https://www.g4atlas.org
 
Description UK-US platform collaborator 
Organisation Purdue University
Department Department of Chemistry
Country United States 
Sector Academic/University 
PI Contribution UK-US platform for the study of RNA structure in living cells
Collaborator Contribution The main scientific objectives: • To forge opportunities for direct communications and knowledge exchange between both experimental scientists and mathematicians/bioinformaticians. • To apply Structure-seq methodologies in yeast and other organisms. • To develop new methods to integrate RNA-protein interaction data with in vivo RNA structural information. • To establish a data-sharing pipeline between UK and USA labs. • To train students and post-docs in both wet-bench experiments and bioinformatics analysis through exchange visits. • To develop and strengthen UK-US collaborations on the functional study of RNA structure in gene regulation through workshops and Skype meetings. • To discover a broad impact of the regulatory role of RNA structure in RNA biology. 1) Prof. Sharon Aviran's lab develops statistical models and statistical inference methods for analysis of RNA structure and dynamics by combining experiments with statistical and biophysical principles. She previously introduced a novel approach to modeling and to automatically processing next-generation sequencing data from a new generation of multiplexed RNA structure mapping assays. This work pioneered the use of mathematical modelling and statistically sound analysis methodology for robust and efficient quantification of chemical mapping information, an approach that is now becoming a standard in the field. She received a K99/R00 award from NIH/NHGRI to pursue work on modelling and analysis of RNA structural dynamics. Prof. Aviran's lab and Dr. Ding's lab have initiated collaborative discussions to develop a novel platform that combines innovative computational and experimental methods. 2) Prof. Elizabeth Tran has established a strong reputation in RNA biology. She has determined the functions of RNA helicases in the regulation of RNA-protein complex that are critically important since DEAD-BOX proteins and regulatory cofactors have been linked to cancer (breast, colon, lung), neurodegenerative disorders, and viral replication (HIV). She has also studied the role of long non-coding RNAs in gene regulation. Prof. Aviran and Dr. Ding recently established informal collaborations with Prof. Tran's lab with initial suggestions on deep sequencing analysis and RNA structure probing techniques. 3) Dr. Zoë Waller's lab has substantial expertise in organic synthesis, biophysics, nucleic acid chemistry and molecular biology. Her lab has been studying one of the well-known structure motifs: i-Motif. She has extensive experience in studying the biophysics and structural dynamics and conformations of non-canonical nucleic acids. She has also generated small molecules to alter the formation of DNA/RNA structure formation; these have great potential in therapeutic and nanotechnology applications. Dr. Waller currently has a BBSRC-funded PhD position (2016) open to study the change of RNA structure motifs in response to stress. Dr. Ding is involved in this PhD program as co-supervisor. Both labs are currently looking for the global structural and biophysical features of RNA from high throughput deep sequencing data. 4) Dr. Yiliang Ding's lab has developed a novel and powerful platform, Structure-seq, to study RNA structure in vivo and across diverse species at the genome-wide scale. Her lab is currently developing new in vivo genome-wide platforms to detect RNA-protein interactions and to simultaneously improve in vivo RNA structure prediction.
Impact The 1st Workshop Program UK-US platform for the study of RNA structure in living cells was from 8th Aug to 10th Aug 2016. It has 21 people from four labs attending this workshop to initiate collaborations.
Start Year 2016
 
Description UK-US platform collaborator 
Organisation University of California, Davis
Department Genome and Biomedical Sciences Facility
Country United States 
Sector Academic/University 
PI Contribution UK-US platform for the study of RNA structure in living cells
Collaborator Contribution The main scientific objectives: • To forge opportunities for direct communications and knowledge exchange between both experimental scientists and mathematicians/bioinformaticians. • To apply Structure-seq methodologies in yeast and other organisms. • To develop new methods to integrate RNA-protein interaction data with in vivo RNA structural information. • To establish a data-sharing pipeline between UK and USA labs. • To train students and post-docs in both wet-bench experiments and bioinformatics analysis through exchange visits. • To develop and strengthen UK-US collaborations on the functional study of RNA structure in gene regulation through workshops and Skype meetings. • To discover a broad impact of the regulatory role of RNA structure in RNA biology. 1) Prof. Sharon Aviran's lab develops statistical models and statistical inference methods for analysis of RNA structure and dynamics by combining experiments with statistical and biophysical principles. She previously introduced a novel approach to modeling and to automatically processing next-generation sequencing data from a new generation of multiplexed RNA structure mapping assays. This work pioneered the use of mathematical modelling and statistically sound analysis methodology for robust and efficient quantification of chemical mapping information, an approach that is now becoming a standard in the field. She received a K99/R00 award from NIH/NHGRI to pursue work on modelling and analysis of RNA structural dynamics. Prof. Aviran's lab and Dr. Ding's lab have initiated collaborative discussions to develop a novel platform that combines innovative computational and experimental methods. 2) Prof. Elizabeth Tran has established a strong reputation in RNA biology. She has determined the functions of RNA helicases in the regulation of RNA-protein complex that are critically important since DEAD-BOX proteins and regulatory cofactors have been linked to cancer (breast, colon, lung), neurodegenerative disorders, and viral replication (HIV). She has also studied the role of long non-coding RNAs in gene regulation. Prof. Aviran and Dr. Ding recently established informal collaborations with Prof. Tran's lab with initial suggestions on deep sequencing analysis and RNA structure probing techniques. 3) Dr. Zoë Waller's lab has substantial expertise in organic synthesis, biophysics, nucleic acid chemistry and molecular biology. Her lab has been studying one of the well-known structure motifs: i-Motif. She has extensive experience in studying the biophysics and structural dynamics and conformations of non-canonical nucleic acids. She has also generated small molecules to alter the formation of DNA/RNA structure formation; these have great potential in therapeutic and nanotechnology applications. Dr. Waller currently has a BBSRC-funded PhD position (2016) open to study the change of RNA structure motifs in response to stress. Dr. Ding is involved in this PhD program as co-supervisor. Both labs are currently looking for the global structural and biophysical features of RNA from high throughput deep sequencing data. 4) Dr. Yiliang Ding's lab has developed a novel and powerful platform, Structure-seq, to study RNA structure in vivo and across diverse species at the genome-wide scale. Her lab is currently developing new in vivo genome-wide platforms to detect RNA-protein interactions and to simultaneously improve in vivo RNA structure prediction.
Impact The 1st Workshop Program UK-US platform for the study of RNA structure in living cells was from 8th Aug to 10th Aug 2016. It has 21 people from four labs attending this workshop to initiate collaborations.
Start Year 2016
 
Description UK-US platform collaborator 
Organisation University of East Anglia
Department School of Environmental Sciences UEA
Country United Kingdom 
Sector Academic/University 
PI Contribution UK-US platform for the study of RNA structure in living cells
Collaborator Contribution The main scientific objectives: • To forge opportunities for direct communications and knowledge exchange between both experimental scientists and mathematicians/bioinformaticians. • To apply Structure-seq methodologies in yeast and other organisms. • To develop new methods to integrate RNA-protein interaction data with in vivo RNA structural information. • To establish a data-sharing pipeline between UK and USA labs. • To train students and post-docs in both wet-bench experiments and bioinformatics analysis through exchange visits. • To develop and strengthen UK-US collaborations on the functional study of RNA structure in gene regulation through workshops and Skype meetings. • To discover a broad impact of the regulatory role of RNA structure in RNA biology. 1) Prof. Sharon Aviran's lab develops statistical models and statistical inference methods for analysis of RNA structure and dynamics by combining experiments with statistical and biophysical principles. She previously introduced a novel approach to modeling and to automatically processing next-generation sequencing data from a new generation of multiplexed RNA structure mapping assays. This work pioneered the use of mathematical modelling and statistically sound analysis methodology for robust and efficient quantification of chemical mapping information, an approach that is now becoming a standard in the field. She received a K99/R00 award from NIH/NHGRI to pursue work on modelling and analysis of RNA structural dynamics. Prof. Aviran's lab and Dr. Ding's lab have initiated collaborative discussions to develop a novel platform that combines innovative computational and experimental methods. 2) Prof. Elizabeth Tran has established a strong reputation in RNA biology. She has determined the functions of RNA helicases in the regulation of RNA-protein complex that are critically important since DEAD-BOX proteins and regulatory cofactors have been linked to cancer (breast, colon, lung), neurodegenerative disorders, and viral replication (HIV). She has also studied the role of long non-coding RNAs in gene regulation. Prof. Aviran and Dr. Ding recently established informal collaborations with Prof. Tran's lab with initial suggestions on deep sequencing analysis and RNA structure probing techniques. 3) Dr. Zoë Waller's lab has substantial expertise in organic synthesis, biophysics, nucleic acid chemistry and molecular biology. Her lab has been studying one of the well-known structure motifs: i-Motif. She has extensive experience in studying the biophysics and structural dynamics and conformations of non-canonical nucleic acids. She has also generated small molecules to alter the formation of DNA/RNA structure formation; these have great potential in therapeutic and nanotechnology applications. Dr. Waller currently has a BBSRC-funded PhD position (2016) open to study the change of RNA structure motifs in response to stress. Dr. Ding is involved in this PhD program as co-supervisor. Both labs are currently looking for the global structural and biophysical features of RNA from high throughput deep sequencing data. 4) Dr. Yiliang Ding's lab has developed a novel and powerful platform, Structure-seq, to study RNA structure in vivo and across diverse species at the genome-wide scale. Her lab is currently developing new in vivo genome-wide platforms to detect RNA-protein interactions and to simultaneously improve in vivo RNA structure prediction.
Impact The 1st Workshop Program UK-US platform for the study of RNA structure in living cells was from 8th Aug to 10th Aug 2016. It has 21 people from four labs attending this workshop to initiate collaborations.
Start Year 2016
 
Description 2nd virtual workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact 18 people attended for the virtual workshop in discussing the collaborative projects.
Year(s) Of Engagement Activity 2021
 
Description 3rd virtual workshops 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact 12 people attended for the workshop
Year(s) Of Engagement Activity 2021
 
Description 4th workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact 18 people attended for the UCL workshop in discussing the collaborative projects.
Year(s) Of Engagement Activity 2017,2018,2019,2020,2021,2022,2023
 
Description Biophysics workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Study participants or study members
Results and Impact Biophysics in person workshop in Norwich with 16 people attended.
Year(s) Of Engagement Activity 2021
 
Description Institute and university visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Two PhD students, Mirko Ledda and Krishna Choudhary from Prof. Sharon Aviran's lab visited John Innes Centre in 2016-2017 to work together on the data processing issues. The meetings were hold at John Innes Centre with 10 lab members from both Dr. Zoe Waller's lab and Dr. Yiliang Ding's lab.
Year(s) Of Engagement Activity 2016,2017
 
Description School Visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Several local discussion meetings were hold between Dr. Zoe Waller's lab and Dr. Yiliang Ding's lab. The discussion on the preliminary data analysis for a BBSRC grant application were hold between the lab members in both labs. Two labs will submit another grant application in 2018.
Year(s) Of Engagement Activity 2017,2018
 
Description The 1st Workshop Program UK-US platform for the study of RNA structure in living cells 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact The 1st Workshop Program UK-US platform for the study of RNA structure in living cells was from 8th Aug to 10th Aug 2016. It has 21 people from four labs attending this workshop to initiate collaborations. We have three-day workshop with 15 excellent talks from the PIs, postdocs and students from the four labs involved in this partnering award.
Year(s) Of Engagement Activity 2016
 
Description The Plant RNA Structure Symposium 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Over 250 people attended for the Plant RNA Structure Symposium 2021.
The 2021 Plant RNA Structure Symposium, will take place from Tuesday 7 September - Thursday 9 September.
It will be hosted online and is being run by the John Innes Centre, in collaboration with the University of Cambridge
RNA structure plays a central role in the post-transcriptional regulation of gene expression, such as RNA maturation, RNA stability, and translation.
With the advance of newly developed RNA structure probing methods, the study of RNA structure has been revolutionarily transformed.
Recent studies have revealed new insights into regulatory mechanisms of RNA biological processes in plants. Furthermore, the identifications of cis-regulatory RNA structure elements in response to temperature and salt stress improved our understanding of how plants adapt to a changing environment.
Apart from these studies in mRNAs, new studies have determined the RNA structure features of different types of non-coding RNAs and discovered how non-coding RNAs function in plants. Additionally, some latest studies in crops have provided novel perceptions in RNA structure evolution and RNA structure-guided crop breeding.

Our plant RNA structure symposium will gather these recent advances in understanding the functional role of RNA structure in plants.

This symposium is sponsored by Frontiers in Plant Science and associated with a special research topic 'Plant RNA Structure' in Frontiers in Plant Science.
Year(s) Of Engagement Activity 2021
URL https://www.jic.ac.uk/event/plant-rna-structure-symposium/
 
Description The RNA Structure Conference 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Over 500 participates attended for the RNA Structure Conference 2021.
The organizers envision that this conference will be unique in many aspects, but in particular will be sharply focused on the state-of-the-art methods being developed to measure RNA structure in living systems and how the merge of chemical probing with transcriptomics has ushered in a new era of characterizing RNA function. In addition, we are aiming to highlight how RNA structure, and our understanding of RNA structure, is informing the design of small molecules that are poised to be next-generation medicines to treat disease.
Year(s) Of Engagement Activity 2021