Why is the highly conserved splicing regulator protein Tra2b essential for spermatogenesis?
Lead Research Organisation:
Newcastle University
Department Name: Biosciences Institute
Abstract
PURPOSE OF RESEARCH: RNA binding proteins like Tra2b play a key role in organising gene expression. This includes the process of alternative splicing through which most single genes produce multiple mRNA splice isoforms. Alternative splicing plays a critical role in building complex animal bodies. Since Tra2b is required for whole animal viability in mice the global targets and pathways it regulates in healthy animals are much less understood compared to its role in cancer cells. The purpose of this research is to address this knowledge gap in the genetically tractable germ cell developmental pathway that makes sperm, and involves cell division by mitosis and meiosis and cell differentiation.
TIMELINESS AND VALUE FOR MONEY: Four aspects of this project are particularly timely. 1) We have an existing conditional Tra2b knockout mouse that we can inactivate within germ cells (in the developmental pathway leading to sperm). Germ cell development is highly active in adult mice yet not essential for viability. Our preliminary work shows that Tra2b is critical for the survival of an important group of germ cells called gonocytes (these are precursors to all other downstream germ cell developmental stages). 2) Through international collaboration with a world leading group in the USA we will be able to identify Tra2b splicing targets in genetically modified germ cells. This collaboration has already enabled us to identify initial splicing targets for Tra2b within gonocytes, and will also help us later in the project. 3) We have identified several million RNA-binding sites for Tra2b using cross linking and next generation sequencing. 4) The MRC unit at Harwell are making a mouse model that will enable us to probe the function of a splicing feedback pathway that controls expression levels of Tra2b and is up-regulated in the testis. This model will later be generally available, but there is a window of opportunity where we will have sole access and can make a really important contribution to understanding why this feedback pathway is important.
AIMS AND OBJECTIVES: This project will decipher how the splicing activity of Tra2b controls germ cell development. Our first objective will be to identify splicing targets controlled by Tra2b in gonocytes, and to analyse these to identify gene expression pathways important for gonocyte survival. Our second objective will be to identify targets for Tra2b during meiosis. We want to do this since Tra2b is up-regulated at meiosis. Our RNA-binding data predicts that Tra2b controls important meiotic genes, and predicts mechanisms of Tra2b splicing control that we want to globally test. Our third objective is to test how Tra2b splicing activity during meiosis is controlled by a splicing feedback control pathway. This splicing feedback control involves an ultraconserved region of the genome indicating it is very important, and is very active in meiotic cells, yet it has not been functionally investigated within an animal model. We predict that this feedback control pathway might either stabilise normal patterns of meiotic splicing control by Tra2b, or alternatively might prevent Tra2b levels increasing to a point where they can damage the transcriptome.
OUTCOMES: We expect that the results of this project will be significant in understanding how splicing factors function to enable flexible use of information in the genome, the development of complex tissues like the testis, and specialised cell types like those undergoing meiosis. Our project will discover new regulated targets of splicing control, and interrogate mechanisms of regulation and phenotypic consequences when this is blocked. The main beneficiaries from this work will be scientists interested in gene expression, scientists and students who will be trained and members of the public that we will engage.
TIMELINESS AND VALUE FOR MONEY: Four aspects of this project are particularly timely. 1) We have an existing conditional Tra2b knockout mouse that we can inactivate within germ cells (in the developmental pathway leading to sperm). Germ cell development is highly active in adult mice yet not essential for viability. Our preliminary work shows that Tra2b is critical for the survival of an important group of germ cells called gonocytes (these are precursors to all other downstream germ cell developmental stages). 2) Through international collaboration with a world leading group in the USA we will be able to identify Tra2b splicing targets in genetically modified germ cells. This collaboration has already enabled us to identify initial splicing targets for Tra2b within gonocytes, and will also help us later in the project. 3) We have identified several million RNA-binding sites for Tra2b using cross linking and next generation sequencing. 4) The MRC unit at Harwell are making a mouse model that will enable us to probe the function of a splicing feedback pathway that controls expression levels of Tra2b and is up-regulated in the testis. This model will later be generally available, but there is a window of opportunity where we will have sole access and can make a really important contribution to understanding why this feedback pathway is important.
AIMS AND OBJECTIVES: This project will decipher how the splicing activity of Tra2b controls germ cell development. Our first objective will be to identify splicing targets controlled by Tra2b in gonocytes, and to analyse these to identify gene expression pathways important for gonocyte survival. Our second objective will be to identify targets for Tra2b during meiosis. We want to do this since Tra2b is up-regulated at meiosis. Our RNA-binding data predicts that Tra2b controls important meiotic genes, and predicts mechanisms of Tra2b splicing control that we want to globally test. Our third objective is to test how Tra2b splicing activity during meiosis is controlled by a splicing feedback control pathway. This splicing feedback control involves an ultraconserved region of the genome indicating it is very important, and is very active in meiotic cells, yet it has not been functionally investigated within an animal model. We predict that this feedback control pathway might either stabilise normal patterns of meiotic splicing control by Tra2b, or alternatively might prevent Tra2b levels increasing to a point where they can damage the transcriptome.
OUTCOMES: We expect that the results of this project will be significant in understanding how splicing factors function to enable flexible use of information in the genome, the development of complex tissues like the testis, and specialised cell types like those undergoing meiosis. Our project will discover new regulated targets of splicing control, and interrogate mechanisms of regulation and phenotypic consequences when this is blocked. The main beneficiaries from this work will be scientists interested in gene expression, scientists and students who will be trained and members of the public that we will engage.
Technical Summary
This project will decipher the role of the splicing regulator protein Tra2b during the germ cell development pathway that creates sperm. Germ cells are non-essential for viability and the first developmental wave after birth is synchronous. This means we can easily monitor effects of Tra2b deletion on cell types and molecular targets. Preliminary global RNA-binding site data from adult testis predicts that Tra2b regulates genes important for germ cell development. To test this we will use conditional mouse models where we can inactivate production of Tra2b protein in any germ cell type, and monitor effects on cell types using histology and gene expression by RNAseq. Our preliminary data shows Tra2b expression is critical for gonocyte survival, and has identified a small group of splicing targets in genes that control RNA biology and transposable element activity. We will complete identification of target exons controlled by Tra2b in gonocytes, confirm Tra2b binding patterns using gel shifts, and test for effects on encoded proteins and downstream pathways that could be important in gonocyte biology. Tra2b expression increases as cells enter meiosis. In our second aim we will test why this is important by inactivating Tra2b during meiotic prophase. We will use histology to monitor the cellular effects of losing Tra2b on meiosis, and RNAseq to identify the genes, cellular pathways and downstream proteins controlled by Tra2b during meiosis. Our final aim will be to identify the function of a highly conserved splicing feedback control pathway that is conserved in all vertebrates. This feedback pathway is highly active in the testis, and we predict will be important to ensure either stable mRNA splice isoform production during meiosis, or to protect the overall integrity of the transcriptome. We will test this using a new mouse model being made for us by the GEMM programme, analysing the function of this poison exon in meiosis using histology and RNAseq.
Planned Impact
BENEFIT TO SOCIETY
WHO WILL BENEFIT. We will contribute to cultural enrichment, by reaching out to local organisations interested in science and schools. We expect male infertility to be of interest to the public and the press.
HOW WILL SOCIETY BENEFIT FROM THIS RESEARCH? We will provide talks to the general public about this project (Café Scientifique, Year 3). We will host sixth form students who are interested in a career in science or medicine, give talks at Science and Engineering weeks at local schools, and issue press releases with papers. We will participate in our IGM flagship event Genetics Matters held every February/March (Years 1-3 of grant).
DELIVERING AND TRAINING HIGHLY SKILLED RESEARCHERS.
WHO WILL BENEFIT? Professional scientists working on this project and students at Newcastle University.
HOW WILL TRAINING BENEFIT FROM THIS RESEARCH? This project will enhance the professional research skills of Caroline Dalgliesh, who is named Researcher on this project, and who will interact with our colleagues in the USA, and local bioinformatics support to analyse RNAseq data sets. A further important training impact of our work will be in science education. Newcastle University is a research-led university, and work in the lab feeds through into taught classes as well as projects carried out by undergraduate and postgraduate students. In the case of lab-based projects, students get the opportunity to become directly involved in research projects. Both the PI and Researcher on this grant are involved in student project supervision. The impact in science education from this grant will be immediate (with undergraduate projects in Years 1-3). As an illustration, our recent BBSRC grant resulted in a paper in Cell Reports that included work from an undergraduate student that was sufficiently important for her to be a co-author. We will similarly engage future students. Caroline will also be involved in training of PhD students including our new BBSRC DTP student.
BENEFIT TO MEN WITH MALE INFERTILITY
WHO WILL BENEFIT? Infertile men with arrested meiosis are frequently seen in clinics, but there is very little that can be done to diagnose or otherwise help them apart from Y chromosome deletion mapping. Although not life threatening, infertility can be psychologically damaging, particularly if it is of unknown origin.
HOW WILL PATIENTS AND CLINICIANS BENEFIT? Although our project is primarily scientific and involves searching for pathways of gene expression that are important for germ cell development in mice, we will also interact with colleagues within our institute who are investigating human male infertility, and our local IVF clinic which is located next door and employs clinicians treating male infertility. These interactions will enable any overlaps in genes and pathways important both in mouse germ cell development and human infertility to be identified. As a result of these interactions, in the long term it is possible that the research in this grant could therefore increase efficiency within the NHS, influence medical practitioners, and be of potential application in the development of diagnostic kits.
BENEFIT TO SCIENTISTS INTERESTED IN DRUG DEVELOPMENT
WHO WILL BENEFIT? Several studies have shown Tra2b to be upregulated in cancer cells suggesting it as a possible future therapeutic target.
HOW WILL STUDY OF TRA2B LEAD TO THIS BENEFIT? Tra2b functions in cancer cells have been globally characterised, and include roles in DNA damage responses that could be important for modulating responses to chemotherapy. However, the normal physiological targets of Tra2b within healthy cells are much less well understood. Yet if Tra2b is to be considered as a possible therapeutic target in cancer it is crucially important to understand these normal physiological functions within healthy animals.
WHO WILL BENEFIT. We will contribute to cultural enrichment, by reaching out to local organisations interested in science and schools. We expect male infertility to be of interest to the public and the press.
HOW WILL SOCIETY BENEFIT FROM THIS RESEARCH? We will provide talks to the general public about this project (Café Scientifique, Year 3). We will host sixth form students who are interested in a career in science or medicine, give talks at Science and Engineering weeks at local schools, and issue press releases with papers. We will participate in our IGM flagship event Genetics Matters held every February/March (Years 1-3 of grant).
DELIVERING AND TRAINING HIGHLY SKILLED RESEARCHERS.
WHO WILL BENEFIT? Professional scientists working on this project and students at Newcastle University.
HOW WILL TRAINING BENEFIT FROM THIS RESEARCH? This project will enhance the professional research skills of Caroline Dalgliesh, who is named Researcher on this project, and who will interact with our colleagues in the USA, and local bioinformatics support to analyse RNAseq data sets. A further important training impact of our work will be in science education. Newcastle University is a research-led university, and work in the lab feeds through into taught classes as well as projects carried out by undergraduate and postgraduate students. In the case of lab-based projects, students get the opportunity to become directly involved in research projects. Both the PI and Researcher on this grant are involved in student project supervision. The impact in science education from this grant will be immediate (with undergraduate projects in Years 1-3). As an illustration, our recent BBSRC grant resulted in a paper in Cell Reports that included work from an undergraduate student that was sufficiently important for her to be a co-author. We will similarly engage future students. Caroline will also be involved in training of PhD students including our new BBSRC DTP student.
BENEFIT TO MEN WITH MALE INFERTILITY
WHO WILL BENEFIT? Infertile men with arrested meiosis are frequently seen in clinics, but there is very little that can be done to diagnose or otherwise help them apart from Y chromosome deletion mapping. Although not life threatening, infertility can be psychologically damaging, particularly if it is of unknown origin.
HOW WILL PATIENTS AND CLINICIANS BENEFIT? Although our project is primarily scientific and involves searching for pathways of gene expression that are important for germ cell development in mice, we will also interact with colleagues within our institute who are investigating human male infertility, and our local IVF clinic which is located next door and employs clinicians treating male infertility. These interactions will enable any overlaps in genes and pathways important both in mouse germ cell development and human infertility to be identified. As a result of these interactions, in the long term it is possible that the research in this grant could therefore increase efficiency within the NHS, influence medical practitioners, and be of potential application in the development of diagnostic kits.
BENEFIT TO SCIENTISTS INTERESTED IN DRUG DEVELOPMENT
WHO WILL BENEFIT? Several studies have shown Tra2b to be upregulated in cancer cells suggesting it as a possible future therapeutic target.
HOW WILL STUDY OF TRA2B LEAD TO THIS BENEFIT? Tra2b functions in cancer cells have been globally characterised, and include roles in DNA damage responses that could be important for modulating responses to chemotherapy. However, the normal physiological targets of Tra2b within healthy cells are much less well understood. Yet if Tra2b is to be considered as a possible therapeutic target in cancer it is crucially important to understand these normal physiological functions within healthy animals.
Organisations
- Newcastle University (Lead Research Organisation)
- University Hospital Center of Saint-Étienne (Collaboration)
- University of Chile (Collaboration)
- University of Southern Denmark (Collaboration)
- University of California, Los Angeles (UCLA) (Collaboration)
- University of East Anglia (Collaboration)
- Tel Aviv University (Collaboration)
- UNIVERSITY OF EXETER (Collaboration)
- University of Cologne (Collaboration)
- University of Pennsylvania (Collaboration)
- Northwestern University (Collaboration)
- Ruhr University Bochum (Collaboration)
- University of Florence (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Utrecht University (Collaboration)
People |
ORCID iD |
David Elliott (Principal Investigator) |
Publications
Advani R
(2023)
Epithelial specific splicing regulator proteins as emerging oncogenes in aggressive prostate cancer.
in Oncogene
Aldalaqan S
(2022)
Cryptic splicing: common pathological mechanisms involved in male infertility and neuronal diseases.
in Cell cycle (Georgetown, Tex.)
Elliott DJ
(2019)
RBMX family proteins connect the fields of nuclear RNA processing, disease and sex chromosome biology.
in The international journal of biochemistry & cell biology
Garnham R
(2024)
ST3 beta-galactoside alpha-2,3-sialyltransferase 1 (ST3Gal1) synthesis of Siglec ligands mediates anti-tumour immunity in prostate cancer.
in Communications biology
Green D
(2023)
YBX1-interacting small RNAs and RUNX2 can be blocked in primary bone cancer using CADD522.
in Journal of bone oncology
Munkley J
(2019)
Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer.
in eLife
Oud MS
(2022)
A de novo paradigm for male infertility.
in Nature communications
Ramond F
(2023)
Clustered variants in the 5' coding region of TRA2B cause a distinctive neurodevelopmental syndrome.
in Genetics in medicine : official journal of the American College of Medical Genetics
Description | This project investigated patterns of gene expression controlled by the RNA splicing regulator protein Tra2beta in the developmental pathway leading to sperm. We used genetically engineered mice to do this project, as the cell types we wanted to look at need to be studied within tissue (they are difficult to model outside the organism). This project was affected by Covid so took a bit longer. However we identified a very interesting phenotype when we inactivated either the entire Tra2b gene, or snipped out a small part of it called a poison exon. We were able to isolate testes from mice without this poison exon, and identify gene expression that depend on the poison exon using a global approach called RNAseq. This is the first animal model that has been developed to test poison exon function, and this work is currently under revision for publication, and will include new global datasets. We also found that the whole gene is important for germline development, but we also had some problems in maintaining these latter mice. This work is currently under revision for a journal. |
Exploitation Route | Information about male infertility will be important for clinicians and infertile men. We hope some of the data that we generate will be helpful to clinicians, as it will point towards pathways that are important for normal male fertility. |
Sectors | Education Healthcare |
Description | We have had school students visit the lab, and we have visited schools. We have also contributed to more general outreach activities. |
First Year Of Impact | 2019 |
Sector | Education |
Impact Types | Cultural Societal |
Title | RNAseq data from P12 mouse testis that are engineered for the Tra2b poison exon |
Description | We have carried out RNAseq analysis of mouse testis after deletion of the Tra2b poison exon, and also wild type mouse testis. |
Type Of Material | Biological samples |
Year Produced | 2023 |
Provided To Others? | No |
Impact | This has enabled us to determine the functions of the Tra2b poison exon. This work is currently under revision. |
Title | conditional mouse line for mouse Tra2b poison exon |
Description | we have made a new mouse model that can be used to inactivate a feedback pathway in any tissue |
Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
Year Produced | 2019 |
Provided To Others? | No |
Impact | We have made a new mouse model where we can inactivate feedback control for the RNA binding protein we are investigating in this grant. We have shown this works, and are now characterising the resulting mice. This is currently under revision. |
Title | iCLIP map of Tra2b binding sites in the adult mouse testis |
Description | We have mapped RNA binding sites for tra2b in the mouse testis |
Type Of Material | Database/Collection of data |
Year Produced | 2014 |
Provided To Others? | No |
Impact | We are using this database to interpret our data. This dataset is currently under revision. |
Description | Collaboration on RNA-protein interactions important for bone metastasis |
Organisation | University of East Anglia |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We carried out iCLIP analysis of YBX1 in a bone cancer cell line. This identified binding to the 3' end of the mRNA encoding the transcription factor RUNX2 that is important in bone cancer. We did the bioinformatic analysis of the iCLIP study. |
Collaborator Contribution | Our collaborator initiated the research project, identified YBX1 as a target for iCLIP analysis, and did the downstream experiments. |
Impact | This study is currently about to be published and is available online at the link https://doi.org/10.1016/j.jbo.2023.100474 |
Start Year | 2019 |
Description | Collaboration with MRC Human Genetics Unit in Edinburgh |
Organisation | Medical Research Council (MRC) |
Department | MRC Human Genetics Unit |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have generated mice that we have characterised using expertise that we learnt through this collaboration |
Collaborator Contribution | Ian adams at the Edinburgh MRC Human Genetics Unit taught us over the last year to analyse mouse seminiferous tubules by staging, and we have been using this information to analyse mouse mutants that we have made that are altered for Tra2b alleles. |
Impact | We have papers in preparation that will include this kind of analysis |
Start Year | 2022 |
Description | Collaboration with University of Cologne |
Organisation | University of Cologne |
Country | Germany |
Sector | Academic/University |
PI Contribution | We have been analysing the effect of deleting the Tra2b gene on mouse testis development |
Collaborator Contribution | The Cologne group provided us with the conditional knockout mouse |
Impact | Academic output: we have been analysing the effects of the Tra2b gene in the germline |
Start Year | 2011 |
Description | Collaboration with University of Pennsylvania |
Organisation | University of Pennsylvania |
Country | United States |
Sector | Academic/University |
PI Contribution | Generation of NGS data and validation of results |
Collaborator Contribution | Analysis of NGS data using cutting edge algorithm |
Impact | This is still in progress currently |
Start Year | 2017 |
Description | Collaboration with Utrecht University |
Organisation | Utrecht University |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | We produced the mice for this collaboration |
Collaborator Contribution | Dirk de Rooij helped us identify cell types in the testis using histology. This helped pinpoint the exact stages that are affected by our mutation. |
Impact | This collaboration was published in eLife, and the publications is in the relevant output in research fish. This collaboration is still ongoing for more recent phenotypes we have discovered |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | Northwestern University |
Department | Feinberg School of Medicine |
Country | United States |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | Ruhr University Bochum |
Country | Germany |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | Tel Aviv University |
Country | Israel |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University Hospital Center of Saint-Étienne |
Country | France |
Sector | Hospitals |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University of California, Los Angeles (UCLA) |
Country | United States |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University of Chile |
Country | Chile |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University of Exeter |
Department | Medical School |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University of Florence |
Country | Italy |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Collaboration with worldwide group of human geneticists |
Organisation | University of Southern Denmark |
Country | Denmark |
Sector | Academic/University |
PI Contribution | We collaborated through our interest in the splicing regulator protein Tra2b. A group of human geneticists were identifying potential loss of function variants in the TRA2B gene. We worked with them to characterise Tra2b expression and splicing patterns in these patients. This involved growing cell lines, doing RNA and protein analyses, and some minigene transfection studies. |
Collaborator Contribution | Our collaborators identified patients with Tra2b variant sequences that had a novel neurodevelopmental disorder by exome sequencing. They also collected cell lines from some patients. |
Impact | We published a paper in the journal Genetics in Medicine |
Start Year | 2017 |
Description | Genome editing in mice for medicine GEMM2 call |
Organisation | Medical Research Council (MRC) |
Department | The Mary Lyon Centre |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We helped design the mouse modification |
Collaborator Contribution | MRC Harwell is made a genetically modified mouse for us using CRISPR |
Impact | We had a successful BBSRC grant awarded to analyse this mouse |
Start Year | 2017 |
Description | Genetics Matters |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | There was very good attendance for this event -108 people were registered. I discussed our BBSRC funded work at a research table, and displayed some of our data. I also showed attendees some microscope slides of human and mouse testes stained for hnRNP GT. Most people attended my table at some point, and there were both questions and discussion. |
Year(s) Of Engagement Activity | 2018,2022,2023,2024 |
Description | Interview for international magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I was interviewed by Newsweek based on the press being aware of the work we published from this grant on male infertility. |
Year(s) Of Engagement Activity | 2019 |
URL | https://www.newsweek.com/picking-sex-baby-scientists-x-ychromosome-sperm-implications-1453756 |
Description | Participation in outreach activity aimed at general public |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | A number of students attended this, and we have already received requests for some to spend more time with us over the summer in work placements. |
Year(s) Of Engagement Activity | 2023,2024 |
URL | https://ney-genomics.org.uk/genetics-matters-free-event-for-rare-disease-day-26th-feb-2023/ |
Description | Visiting school to talk about science |
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 | The school were really grateful to my BBSRC funded student and Path Society student for teaching them molecular biology techniques for a day, and providing careers advice |
Year(s) Of Engagement Activity | 2019 |
URL | https://twitter.com/HA_BiologyDept/status/1181283062086275072 |
Description | lab twitter account |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | We report events in the lab - talks, papers, visits |
Year(s) Of Engagement Activity | 2018,2019,2020,2021,2022,2023,2024 |
URL | https://twitter.com/TheElliottLab |
Description | visit from high school students for work experience |
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 | 3 students did their work experience placement with us. They reported that it helped them make decisions about careers and university courses. We designed the placements so that the students got a broad range of experience, sharing between participating labs. The school and parents were very grateful for the work we did with them. |
Year(s) Of Engagement Activity | 2019,2020,2022,2023 |
Description | visiting school to talk about research and careers in science |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | The school were very grateful for our efforts in organising this event, which was attended by the A level biology class "Thank you so much for your presentation this afternoon. It was really good for the students (and me) to hear about how the science they learn in the lab is relevant in the real world and I also very much enjoyed the content. It was well attended despite the ski trip meting and I think that reflects the interest our pupils have for science, something I'm keen to promote. Alice and Chile were a great addition and spoke passionately about their role as researcher and they were excellent role models for the girls who attended." |
Year(s) Of Engagement Activity | 2019 |
URL | https://twitter.com/TheElliottLab/status/1201910825897938944 |