Regulation and functions of male-derived shed microvesicles in Drosophila reproduction
Lead Research Organisation:
University of Oxford
Department Name: Physiology Anatomy and Genetics
Abstract
Although males and females share a common goal when they mate, the production of offspring who carry copies of their genes, there is at the same time an important conflict between them. While on the one hand, males of many species can best maintain their gene pool by mating with many females and preventing other males from competing, females are often best served by sampling sperm from multiple males. Three years ago, we started to study the ways in which males have adapted to fight this battle of the sexes. We speculated that males had developed specialised ways of delivering signals to females that made their sperm work at their best and also stopped other males from mating with these females. We decided to work with the fruit fly, partly because it was already known that male flies had developed ingenious ways to fight the reproductive battle. They assemble a plug in the female uterus that blocks remating and also alter female behaviour so she rejects subsequent advances from other males. Flies are ideal for studies of this kind because they can be easily manipulated to identify the genes involved and find out how they work. About 70% of all genes known to be involved in human disease are also found in flies. Lots of the basic mechanisms in human biology were originally studied in flies or other simple organisms before being looked at in humans.
We are studying a male gland in flies called the accessory gland that seems to share many features of the human prostate and seminal vesicles, which generate most of the main components of semen. We have already shown that one type of cell in this gland secretes tiny membrane-bound packages that are passed into females on mating and fuse to sperm. These packages, called exosomes, are required to alter female behaviour after mating. Remarkably the human prostate also produces exosomes that fuse to sperm. Our work is starting to reveal how these exosomes are made and how they affect sperm, and we are beginning to see how defects in exosome production might be involved in aspects of prostate cancer, ideas that we are now following up with clinical colleagues.
Recently we discovered that another type of cell in the accessory gland secretes larger membrane-bound structures called shed microvesicles (SMVs) that are also passed to females in huge numbers during mating. These vesicles carry several key proteins that are already known to drive changes in the female after mating, like increased egg laying, sperm storage, mating plug formation and altered remating behaviour. SMVs coalesce to make a mating plug in one part of the female reproductive tract, while in other parts, they remain intact, but release one of their attached proteins, which then binds to sperm and allows it to be stored. These SMVs may also bind to female cells, raising the possibility that they could communicate to females in this way.
Several important fly molecules involved in this process are related to mammalian reproductive proteins. In fact, the discovery of SMVs in fly semen explains a mystery in both fly and mammalian reproduction - several proteins secreted into semen look like they should be attached to membranes, and not secreted. We will study how SMVs are made, work out what they do in females after mating and how these events are controlled by proteins made in the accessory gland. This work will not only help us to understand fundamental principles of reproduction, it may give us new ideas for reproductive therapies and contraception. SMVs are also important in blood clotting, inflammation and growth. We have evidence that the basic controls on these different processes are similar, opening up the possibility that our work will provide new insights into diseases where these processes go wrong. Our proposed work, looking into an important, but previously intractable problem, may therefore impact on several areas of biology relevant to human health.
We are studying a male gland in flies called the accessory gland that seems to share many features of the human prostate and seminal vesicles, which generate most of the main components of semen. We have already shown that one type of cell in this gland secretes tiny membrane-bound packages that are passed into females on mating and fuse to sperm. These packages, called exosomes, are required to alter female behaviour after mating. Remarkably the human prostate also produces exosomes that fuse to sperm. Our work is starting to reveal how these exosomes are made and how they affect sperm, and we are beginning to see how defects in exosome production might be involved in aspects of prostate cancer, ideas that we are now following up with clinical colleagues.
Recently we discovered that another type of cell in the accessory gland secretes larger membrane-bound structures called shed microvesicles (SMVs) that are also passed to females in huge numbers during mating. These vesicles carry several key proteins that are already known to drive changes in the female after mating, like increased egg laying, sperm storage, mating plug formation and altered remating behaviour. SMVs coalesce to make a mating plug in one part of the female reproductive tract, while in other parts, they remain intact, but release one of their attached proteins, which then binds to sperm and allows it to be stored. These SMVs may also bind to female cells, raising the possibility that they could communicate to females in this way.
Several important fly molecules involved in this process are related to mammalian reproductive proteins. In fact, the discovery of SMVs in fly semen explains a mystery in both fly and mammalian reproduction - several proteins secreted into semen look like they should be attached to membranes, and not secreted. We will study how SMVs are made, work out what they do in females after mating and how these events are controlled by proteins made in the accessory gland. This work will not only help us to understand fundamental principles of reproduction, it may give us new ideas for reproductive therapies and contraception. SMVs are also important in blood clotting, inflammation and growth. We have evidence that the basic controls on these different processes are similar, opening up the possibility that our work will provide new insights into diseases where these processes go wrong. Our proposed work, looking into an important, but previously intractable problem, may therefore impact on several areas of biology relevant to human health.
Technical Summary
When males mate, they must deliver sperm and a diverse range of seminal proteins to different parts of the female reproductive tract that fulfil several key reproductive functions. In studying this process in flies, we discovered that epithelial cells in the male accessory gland (AG) produce shed microvesicles (SMVs) that carry key seminal proteins into females. We have developed genetic tools to analyse the biogenesis and functions of these SMVs in the AG, which we will combine with available mutants, cell type-specific knockdown and overexpression to genetically analyse SMV biology in fly reproduction. Our key objectives are to:
1. genetically dissect the process of SMV biogenesis by screening a series of very strong candidate genes identified through microarray analysis;
2. identify the genes that target SMVs to different regions of the female reproductive tract and that then allow release of effector proteins from these vesicles, which promote sperm storage, suppress immune responses and alter female behaviour;
3. determine the functions of SMVs in reproduction by genetically blocking their secretion, using the tools developed in our first objective.
Several of the key molecules expressed by the AG that are vital for male reproduction have already been characterised genetically. However, our data suggest that these proteins interact with SMVs to perform their functions. Our proposed study should elucidate the roles of SMVs in these processes and determine how their interactions with seminal proteins change after mating. SMVs are not only implicated in reproduction, but also in blood coagulation, inflammation and diseases such as cancer, so our ability to study their function in a system that can be easily genetically manipulated may provide significant insights into several processes that rely on these poorly studied signalling structures.
1. genetically dissect the process of SMV biogenesis by screening a series of very strong candidate genes identified through microarray analysis;
2. identify the genes that target SMVs to different regions of the female reproductive tract and that then allow release of effector proteins from these vesicles, which promote sperm storage, suppress immune responses and alter female behaviour;
3. determine the functions of SMVs in reproduction by genetically blocking their secretion, using the tools developed in our first objective.
Several of the key molecules expressed by the AG that are vital for male reproduction have already been characterised genetically. However, our data suggest that these proteins interact with SMVs to perform their functions. Our proposed study should elucidate the roles of SMVs in these processes and determine how their interactions with seminal proteins change after mating. SMVs are not only implicated in reproduction, but also in blood coagulation, inflammation and diseases such as cancer, so our ability to study their function in a system that can be easily genetically manipulated may provide significant insights into several processes that rely on these poorly studied signalling structures.
Planned Impact
Potential beneficiaries in academia are outlined in the previous section. Our work has wide-ranging implications, given the postulated roles of SMVs in animal biology, and their potential uses for biodelivery of drugs. We have indicated in the previous section how our work could be developed in academia within these areas.
Other areas of potential impact are:
1. Clinical Medicine
Key findings that could emerge from our work are the identification of : i. molecular genetic mechanisms by which SMVs are formed in secreting cells; ii. molecular genetic mechanisms controlling SMV coagulation; iii. general molecular mechanisms by which SMVs release attached proteins (eg., SP, Acp36DE); iv. molecular genetic mechanisms promoting SMV attachment to cell membranes and potential crossing of epithelia. As discussed in the previous section, the knowledge gained from these studies could ultimately impact on the clinic in several areas, such as reproductive medicine, blood coagulation and inflammation. Although SMVs are implicated in all these processes, we know remarkably little about several aspects of their basic biology, so at this point, it is really difficult to determine what the impact of our studies will be. But our link with Ian Sargent, a key figure in Oxford in the clinical exosome and SMV fields, will allow us to make contact with the appropriate group of clinicians to take any discoveries forward.
2. Pharmaceutical Industry and Biotechnology
As discussed above, the translation of our work into human systems may suggest new ways of intervening in processes like blood coagulation, which are believed to be initiated by SMV signals, although this is likely to be a relatively long-term goal. But if we learn how SMV secretion is controlled through our studies, and how these structures deliver their contents to the appropriate target site, this could suggest very novel ways to target hydrophobic or hydrophilic drugs to specific sites in the body. Again, at present the possibilities are tantalising because this is such an unexplored area. It is not possible at present to develop concrete ideas of how our work may impact in these areas, but our contacts with the Wood lab should allow us to exploit opportunities as they arise.
It is possible that SMVs could deliver novel compounds to females during insect reproduction. Although we think it will probably be too costly to develop this commercially, we will explore this possibility with colleagues in this area.
3. General Public and Schools
We think it is important to disseminate our work to a wider public for two main reasons. First, our studies are frequently targeted at fundamental problems that are ultimately relevant to human health. Our experience is that this generates significant interest in the media. We think the main theme of our work, that males release packages of active molecules to reprogramme female behaviour and optimise male fecundity, will be both surprising and fascinating to the public, particularly if there are clinical implications. And the fact that we can visualise SMVs should spark the imagination of an audience that knows very little about these structures at present. Potentially it might even have controversial implications concerning the biological interactions between men and women. Second, our work has advantages in the context of the 3Rs (replacement). We strongly believe that aspects of physiological research must be pursued in vivo, and our work exemplifies how simpler organisms can avoid some of the potential ethical issues, while answering questions of fundamental importance to human and other animal health.
Other areas of potential impact are:
1. Clinical Medicine
Key findings that could emerge from our work are the identification of : i. molecular genetic mechanisms by which SMVs are formed in secreting cells; ii. molecular genetic mechanisms controlling SMV coagulation; iii. general molecular mechanisms by which SMVs release attached proteins (eg., SP, Acp36DE); iv. molecular genetic mechanisms promoting SMV attachment to cell membranes and potential crossing of epithelia. As discussed in the previous section, the knowledge gained from these studies could ultimately impact on the clinic in several areas, such as reproductive medicine, blood coagulation and inflammation. Although SMVs are implicated in all these processes, we know remarkably little about several aspects of their basic biology, so at this point, it is really difficult to determine what the impact of our studies will be. But our link with Ian Sargent, a key figure in Oxford in the clinical exosome and SMV fields, will allow us to make contact with the appropriate group of clinicians to take any discoveries forward.
2. Pharmaceutical Industry and Biotechnology
As discussed above, the translation of our work into human systems may suggest new ways of intervening in processes like blood coagulation, which are believed to be initiated by SMV signals, although this is likely to be a relatively long-term goal. But if we learn how SMV secretion is controlled through our studies, and how these structures deliver their contents to the appropriate target site, this could suggest very novel ways to target hydrophobic or hydrophilic drugs to specific sites in the body. Again, at present the possibilities are tantalising because this is such an unexplored area. It is not possible at present to develop concrete ideas of how our work may impact in these areas, but our contacts with the Wood lab should allow us to exploit opportunities as they arise.
It is possible that SMVs could deliver novel compounds to females during insect reproduction. Although we think it will probably be too costly to develop this commercially, we will explore this possibility with colleagues in this area.
3. General Public and Schools
We think it is important to disseminate our work to a wider public for two main reasons. First, our studies are frequently targeted at fundamental problems that are ultimately relevant to human health. Our experience is that this generates significant interest in the media. We think the main theme of our work, that males release packages of active molecules to reprogramme female behaviour and optimise male fecundity, will be both surprising and fascinating to the public, particularly if there are clinical implications. And the fact that we can visualise SMVs should spark the imagination of an audience that knows very little about these structures at present. Potentially it might even have controversial implications concerning the biological interactions between men and women. Second, our work has advantages in the context of the 3Rs (replacement). We strongly believe that aspects of physiological research must be pursued in vivo, and our work exemplifies how simpler organisms can avoid some of the potential ethical issues, while answering questions of fundamental importance to human and other animal health.
Publications
Goberdhan DC
(2016)
Amino Acid Sensing by mTORC1: Intracellular Transporters Mark the Spot.
in Cell metabolism
Thind A
(2016)
Exosomal miRNAs as cancer biomarkers and therapeutic targets.
in Journal of extracellular vesicles
Redhai S
(2016)
Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells.
in PLoS genetics
Mensah LB
(2017)
mTORC1 signalling mediates PI3K-dependent large lipid droplet accumulation in Drosophila ovarian nurse cells.
in Biology open
Wilson C
(2017)
The Drosophila Accessory Gland as a Model for Prostate Cancer and Other Pathologies.
in Current topics in developmental biology
Théry C
(2018)
ISEV2018 abstract book
in Journal of Extracellular Vesicles
Leiblich A
(2019)
Mating induces switch from hormone-dependent to hormone-independent steroid receptor-mediated growth in Drosophila secondary cells.
in PLoS biology
Description | This grant funded the investigation of lipid-containing cigar-shaped structures, which we had discovered while studying the biology of this gland. These structures, which we now call microcarriers, are released from the epithelial 'main cells' of the Drosophila male accessory gland; we had shown that they carry a key seminal protein involved in changing the behaviour of females after mating called Sex Peptide (SP). Since these structures appear to represent a new form of secretory vehicle, we set out to study how they are regulated and to determine their functions. We have discovered that: 1. microcarriers contain a lipid-rich centre and carry SP on their surface. Following mating, these structures dissipate and release SP, which binds to the plasma membrane of sperm tails and is stored with sperm in the female sperm storage organs. We conclude that one role of microcarriers in the accessory gland is to act as a long term repository for key seminal proteins that are not fully soluble, and then to allow quick release of these proteins when they arrive in the female reproductive tract. 2. microcarrier formation is controlled by SP. SP null mutations and main cell-specific SP knockdown both lead to the production of highly enlarged, fused lipid globules that are no longer properly loaded with their cargos, which become diffusely distributed throughout the defective structures. Therefore SP has a new, previously unrecognised, function in males, the control of microcarrier formation, in addition to its well-established roles when transferred to females. 3. using inducible knockdown, we find that once defective microcarriers are formed in the absence of SP, they cannot recover their structure, even if SP is resupplied. In this latter scenario, males remain unable to induce long-term stimulation of ovulation in females, even though their seminal fluid contains SP. These experiments surprisingly suggest that SP's function in microcarrier biogenesis may explain some of the changes in mated females associated with SP loss in males. 4. a specific lipid metabolic enzyme is essential for normal microcarrier release from main cells, highlighting a very specific aspect of lipid metabolism that is involved in this process and highly upregulated in the main cells. Remarkably the enzyme involved is widely expressed in mammalian secretory cells and has roles in bile secretion, myelination and breast milk, and is frequently upregulated in cancer, suggesting that there may be functions for this new type of secretory vehicle in higher organisms too. The initial work describing the role of SP in microcarrier formation and function has now been published (Wainwright et al., 2021). Publication took more time than anticipated for two reasons: first, because the mechanisms we describe have not been previously reported and we have therefore needed to verify them by multiple approaches; second, because we have found that the classic SP mutant employed in many previous studies appears to carry a second mutation that may affect male fertility, again requiring us to use additional approaches to confirm our findings. |
Exploitation Route | We have identified a new mechanism by which partially soluble molecules can be stored and then delivered to a specific location in response to as yet unidentified cues (ie. in the female reproductive tract). Going forward, we envisage the following: 1. characterisation in mammalian cells of the effects of overexpression of the novel lipid metabolic enzyme we have implicated in microcarrier formation, initially in cell culture, to test whether microcarriers can be formed by these cells; 2. analysis of microcarrier components in flies and humans by proteomics and lipidomics; determine what cargos are required to form normal microcarrier structures; 3. others, including our collaborators, could then test whether this system might be engineered for delivery of specific drugs, etc; 4. other groups or our collaborators could determine whether the microcarrier system might be employed in any pest control strategies, where they are used to deliver a pest control molecule to females in the wild. |
Sectors | Agriculture Food and Drink Healthcare Pharmaceuticals and Medical Biotechnology |
Description | Since 2016, we have presented aspects of our work in several engagement activities, particularly with schoolchildren. They are particularly interested and surprised to hear how using flies can impact our understanding of cancer and basic biological processes involved in human disease. Feedback is routinely positive and some of the individuals who come from schools that have previously very limited links to Oxford have applied here, a key objective of some of the events that we hold. We are now also involved in the UNIQ and UNIQ+ schemes in Oxford, where schoolchildren and undergraduate students from disadvantaged backgrounds come to Oxford to experience the academic opportunities here: schoolchildren stay for a week and receive a range of academic sessions, including a cell biology tutorial that I participate in, and undergraduates work in my lab on accessory gland projects inspired by our funded studies. These students often successfully apply to Oxford (and other world-class Universities) subsequently. |
First Year Of Impact | 2015 |
Sector | Education |
Impact Types | Cultural Societal |
Description | MRC DPhil studentship |
Amount | £110,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2018 |
Description | Regulation and activities of amyloidogenic proteins APP and TGFBI in physiological and pathological protein aggregation |
Amount | £567,179 (GBP) |
Funding ID | BB/W00707X/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2022 |
End | 01/2025 |
Description | Regulation of exosome heterogeneity and function |
Amount | £621,117 (GBP) |
Funding ID | BB/R004862/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2018 |
End | 03/2021 |
Description | Responsive mode award |
Amount | £518,971 (GBP) |
Funding ID | BB/N016300/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 07/2016 |
End | 09/2019 |
Description | Sex Peptide-dependent microcarrier signalling in reproduction |
Amount | £572,207 (GBP) |
Funding ID | BB/W015455/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 11/2022 |
End | 10/2025 |
Description | Wellcome Trust Chromosome and Developmental Biology Programme DPhil studentship |
Amount | £120,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 09/2013 |
End | 09/2017 |
Title | Genetic manipulation that specifically blocks Rab11/Rab11a-exosome biogenesis (accessory ESCRT-III knockdown) |
Description | Studying exosome-secreting Drosophila cells and human cancer cell lines, we have found that inhibiting accessory ESCRT-III proteins selectively blocks the production and secretion of Rab11/Rab11a-exosomes, and using this tool, we have shown that these exosomes, which make up a small proportion of extracellular vesicles secreted by cancer cells, are potent mediators of several functions that ;promote cancer progression and drug resistance, as well as playing key reproductive roles in reproduction. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | This discovery has significantly impacted on studies in my group, primarily because it provides strong evidence that the trafficking pathways we are studying in flies are very highly conserved in mammals, work that has been the impetus for new funding applications and manuscripts that are soon to be submitted. |
URL | https://onlinelibrary.wiley.com/doi/10.1002/jev2.12311 |
Title | Genetic model of dense-core granule secretion and its regulation |
Description | We have developed the Drosophila secondary cell as a new genetic model for dense-core granule (DCG) biogenesis. We have developed new tools to mark DCGs in living cells, eg., GFP-GPI, and used this system to show that BMPs, loaded in DCGs, control secretion in an autocrine fashion. BMPs are implicated in insulin secretory regulation in beta cells and we postulate that similar mechanisms may be involved. Relevant to 3Rs. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | Redhai, S., Hellberg, J.E.E.U., Wainwright, M., Perera, S.W., Castellanos, F., Kroeger, B., Gandy, C., Leiblich, A., Corrigan, L., Hilton, T., Patel, B., Fan, S.-J., Hamdy, F., Goberdhan, D.C.I., Wilson, C. (2016) Regulation of dense-core granule replenishment by autocrine BMP signalling in Drosophila secondary cells. PLoS Genet. 12, e1006366. £518,971 from the BBSRC for a project entitled "Linking reproductive behaviour and dense core granule biogenesis in secondary cells of the Drosophila male reproductive system" Wilson, C. PI. (August 2016 - August 2019). - BB/N016300/1 Several invitations and platform presentations at meetings: 2016 & 2017 US Drosophila Conference. |
Title | New model for insulin signalling-/diet-linked, age-related degenerative disease in Drosophila |
Description | We identified a mutant in tumour suppressor gene Pten, which has an age-related muscle degeneration phenotype and showed that this defect was mTORC1-dependent and reduced mitochondrial integrity. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Provided To Others? | No |
Impact | Mensah LB, Davison C, Fan SJ, Morris JF, Goberdhan DC, Wilson C. (2015). Fine-Tuning of PI3K/AKT Signalling by the Tumour Suppressor PTEN Is Required for Maintenance of Flight Muscle Function and Mitochondrial Integrity in Ageing Adult Drosophila melanogaster. PLoS One 10:e0143818. |
URL | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143818 |
Title | New model to study hormone-independent steroid receptor signalling in prostate-like secondary cells and its physiological functions |
Description | We have shown that growth and genome endoreplication in secondary cells of the Drosophila male accessory gland following mating is regulated by a steroid-independent form of Ecdysone Receptor signalling, which mirrors events that take place in castration-resistant prostate cancer. These results suggest that hormone-independent signalling, at least in the fly system is a physiological process, not just a pathological one, and is induced by increased levels of secretion. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | Our current data suggest that hormone-independent signalling is controlled by some of the signalling pathways implicated in castration-resistant prostate cancer, suggesting there are biological parallels between these two events. |
URL | https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000145 |
Title | Tools to study intracellular and extracellular Rab11-exosomes in vivo in Drosophila |
Description | We identified the source of exosomes made by secondary cells in the Drosophila male accessory gland, which are Rab11-positive compartments, and developed multiple tools to image them in living cells and following secretion. Previously, exosomes were reported to be derived from late endosomes and lysosomes. This system allows us to genetically screen regulators of these so-called Rab11-exosomes by knockdown. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2020 |
Provided To Others? | Yes |
Impact | In the same paper, our collaborators demonstrated that Rab11a-exosomes are made in human cancer cells, and in these cells, they are induced by nutrient-dependent mTORC1 inhibition and have pro-tumorigenic effects that may be linked to tumour adaptation. |
URL | https://www.embopress.org/doi/full/10.15252/embj.2019103009 |
Title | Tools to study microcarriers, new neutral lipid-based secreted vehicles for signalling molecules |
Description | We identified large neutral lipid-based secreted vehicles for signalling molecules such as Sex Peptide in the lumen of the Drosophila male accessory gland. These have been named microcarriers. We developed multiple tools to visualise these in living tissue. We showed that microcarriers play an important role in storing these signalling molecules for days and weeks in the male, but then disperse within minutes when delivered to the female uterus during mating. |
Type Of Material | Model of mechanisms or symptoms - non-mammalian in vivo |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | We have unpublished data suggesting that the formation of microcarriers involves a highly evolutionarily conserved lipid glucosytransferase and comparative studies in humans suggest that these structures may be made in organs like the breast, and upregulated in breast cancer. |
URL | https://www.pnas.org/content/118/5/e2019622118.long |
Title | Comparative proteomics to identify the cargos of Rab11a-exosomes and other stress-induced extracellular vesicle subtypes |
Description | Comparative proteomics using the TMT method, comparing protein cargos of EVs from nutrient-depleted versus nutrient-replete HCT116 colorectal cancer cells, Allowed us to identify Rab11a-exosome cargos that are specifically involved in generation of these vesicles, eg. the accessory ESCRT-III proteins. |
Type Of Material | Database/Collection of data |
Year Produced | 2023 |
Provided To Others? | Yes |
Impact | These data are continuing to inform our analysis of stress-induced extracellular vesicle biogenesis and are directly impacting on our work on protein aggregation and its links to health and disease. |
URL | https://onlinelibrary.wiley.com/doi/10.1002/jev2.12311 |
Title | Proteomics analysis of male accessory glands from wild type and Sex Peptide mutant Drosophila before and after mating to identify microcarrier cargos and regulators |
Description | Proteomics dataset to identify the changes in secretion and microcarrier loading in Sex Peptide mutant males, the first mutant identified where microcarrier formation and loading is disrupted. Reported in Wainwright et al., 2021, PNAS. |
Type Of Material | Database/Collection of data |
Year Produced | 2021 |
Provided To Others? | Yes |
Impact | Identification of several new candidate microcarrier regulators that are now being tested genetically. |
URL | http://central.proteomexchange.org/cgi/GetDataset?ID=PXD021897 |
Description | Cell-cell communication via lncRNA transfer |
Organisation | University of Toronto |
Department | Donnelly Centre for Cellular and Biomolecular Research |
Country | Canada |
Sector | Academic/University |
PI Contribution | Expertise in analysing exosome- and microcarrier-mediated signalling between cells. |
Collaborator Contribution | Expertise in lncRNA expression and function in Drosophila. |
Impact | Canadian Institutes of Health Research grant 2019 - 2024. We will provide training, tools, experimental input and expertise as collaborators in analysing accessory gland cell biology. |
Start Year | 2019 |
Description | ChemiBio Hub meeting - University of Oxford/industry conversation - 31.7.2015 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Type Of Presentation | poster presentation |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Discussions with pharmaceutical company representative at meeting led to subsequent visit to the labs of my collaborator and me and discussion of possible collaborative overlaps. Discussion concerning collaboration and possible translation of our work in progress. |
Year(s) Of Engagement Activity | 2015 |
Description | Medicine & Biomedical Sciences Taster Day, 28 May, 2016 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | We ran a whole day event at St. Hugh's College and our Department for students from schools that rarely send students to Oxford, including introductory talks, a lecture, mock interview, Q&A and then in the afternoon, research demonstrations related to our ongoing research on Drosophila, exosomes, etc. |
Year(s) Of Engagement Activity | 2016 |
Description | Open Days in Oxford (St Hugh's College) for schoolchildren |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Schools |
Results and Impact | I meet small numbers of schoolchildren, typically three times per year to discuss studying at Oxford in medicine and biomedical sciences, and highlighting the importance of research in the Oxford academic environment. I have had school work placements in my lab linked to these sessions. We have also has applications to Oxford from students studying at schools that do not have a history of student applications to Oxford, which I regard as a really important aspect of these Open Day sessions. |
Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2011,2012,2013,2014 |
Description | Press coverage of published work |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | A press release relating to Fan et al. (2015) Oncogene Oct 5. doi: 10.1038/onc.2015.363 was covered in several national newspapers and science websites - Daily Telegraph, Sun, Daily Mirror - http://www.mirror.co.uk/lifestyle/health/cancer-tumours-could-starved-death-6578860, medicaldaily, financialexpress, GoodNewsNetwork, medicalxpress |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.dpag.ox.ac.uk/news/identifying-cancer2019s-food-sensors-may-help-to-halt-tumour-growth |
Description | School Visit (Kent) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Presentation and Q&A session to post-GSCE schoolchildren from a region around St. Olave's Grammar School in Orpington, Kent. Discussing medicine and biomedicine as a degree and career option, admissions to Oxford, etc. After the Q&A session, I answered individual questions from students, two of whom indicated that their views on the most appropriate career choices had changed as a result of the meeting. I also received e-mails of thanks from the co-ordinating teacher at the meeting and some parents. |
Year(s) Of Engagement Activity | 2018,2019 |
Description | School visit (Canterbury) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | About 50 people attended a careers talk and research discussion in biomedicine and medicine talk, which was followed by questions. Also had supper with a few students with specific interests in these areas. School arranged visit to Oxford to discuss opportunities for students to study or undertake projects here. |
Year(s) Of Engagement Activity | 2011,2014 |
Description | School visit to discuss Oxford Medical Course and medical research |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | I gave a talk and Q&A session at a London school to school pupils from a consortium of London schools (City of London Corporation's family of schools), who were interested in studying medicine. The primary function of the presentation was to demystify the Oxford medical course and encourage students from as diverse backgrounds as possible to consider applying to the course. I also discussed the link between basic biomedical research and clinical medicine. |
Year(s) Of Engagement Activity | 2023 |
Description | Super Genes Day - 300 Year 12/13 students - demonstration in Natural History Museum, Oxford, March 18, 2016 |
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 | We ran a 1.5 hour demonstration in the Natural History Museum on Super Genes Day, when 300 Year 12/13 students from schools nationally visit for a full day. We were showing students how flies can be used to study the genetics of biological processes and discussing the development of the fly as a model for prostate biology and cancer, which has been developed in my lab. Interactive displays looking at different fly genotypes, high-resolution imaging data and discussing exosome biology. Spoke to studnets and teachers, some of whom asked for advice on using Drosophila in practicals at school. |
Year(s) Of Engagement Activity | 2016 |
Description | UNIQ Alumni Evening, 26 July 2016 |
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 | I was involved in a event during a UNIQ event over the summer: students from schools that rarely, if ever, send students to Oxford stay in Oxford for a week and are involved in lectures, practical , tutorials and other events to introduce them to what is available here. I chaired an evening where we had a Q&A session for the students and also discussed our academic backgrounds, our research careers and our current research interests. The students were very engaged and many applied to Oxford. |
Year(s) Of Engagement Activity | 2016 |
Description | UNIQ 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 | Education week giving students from disadvantaged backgrounds the opportunity to experience University and Oxford environment and to encourage them to aspire to applying to the top national Universities. I have been involved in a cell biology tutorial session with a group of ~ 6 students, where they can personally interact with academics and I can discuss our work, as well as basic aspects of cell biology. This session is highlighted by most students as the most useful event of the week. More recently, I have also been involved in giving the students a sample first year lecture. We are aware that many student on this course decide to apply to Oxford and they have a success rate that is typically higher than other students. |
Year(s) Of Engagement Activity | 2019,2022,2023 |