Regulation of the proteasome by Fbxo7

Lead Research Organisation: University of Cambridge
Department Name: Pathology

Abstract

Living cells are largely constructed from a multitude of different proteins, each with their own individual functions and properties. Just like the components of any man-made machine, these proteins are susceptible to "wear and tear" and can become damaged over time. The health of a cell, and consequently the whole organism to which it belongs depends on the timely and specific removal of damaged proteins to prevent their accumulation in toxic aggregates that will eventually poison the cell. Cells have evolved a mechanism to identify and then destroy unwanted proteins, called the "ubiquitin-proteasome system". Damaged proteins are marked with chains of small ubiquitin molecules, targeting them to the proteasomes, the cell's "recycling bins". The failure of this system to clear protein aggregates has been linked to multiple human diseases, including Parkinson's disease, Alzheimer's disease, type II diabetes and is also implicated in those involving prion proteins which cause Creutzfeldt-Jakob disease in humans, BSE in cattle and scrapie in sheep and goats. Conversely, over-activity of the ubiquitin-proteasome system has been linked with various muscle atrophy diseases, it is therefore clear that proper regulation of this system is required for the maintenance of health.

Recently, a study detailing the properties of a controller of the rate at which the proteasomes operate has been published. This protein, called PI31, has been shown to both increase and decrease proteasome activity under different circumstances. However, PI31 does not act alone. We have identified a protein called Fbxo7 that is not only capable of marking proteins for destruction with ubiquitin but which also binds to PI31. Studies in fruit flies have shown that this interaction enhances the ability of PI31 to regulate the proteasomes, and flies lacking their analgous Fbxo7 protein, which is called nutcracker, have reduced proteasome activity, and causes sterility in male flies. We have found that loss of the Fbxo7 in mice also affects their fertility. Furthermore, mutations in the human Fbxo7 gene have also been linked to Parkinson's disease, suggesting that Fbxo7 may also cooperate with PI31 to regulate proteasome activity in mammalian systems.

We want to understand in detail how Fbxo7 participates in the regulation of proteasome activity in mammalian cells. We will use a variety of methods to investigate the relationship between PI31 and Fbxo7, determining whether the interaction between these two proteins affects their ability to regulate proteasome activity and mark proteins for degradation, respectively. We will also determine how the loss or over-representation of Fbxo7 in cells affects proteasome activity in cells using a range of assays both in cell lines and in an mouse model. By doing experiments to broaden our understanding of the protein degradation machinery, we hope to be able to affect and ultimately direct these processes in clinically relevant settings.

Technical Summary

The ability to remove damaged proteins to prevent the formation of toxic protein aggregates is essential for cell survival. This function, performed by the ubiquitin-proteasome system (UPS), uses poly-ubiquitin tagging of defective proteins to direct them to the proteasome, a multi-subunit protease. Defects in the UPS are linked to multiple diseases of humans and animals.
Originally identified as a proteasome inhibitor, PI31 has now been shown to enhance proteasome activity in Drosophila when stabilised by the F-box protein nutcracker. Loss of nutcracker expression reduces proteasome activity and causes male sterility. The human orthologue of nutcracker, Fbxo7, also binds PI31. It also acts as a substrate-recruiting subunit for an SCF-type ubiquitin ligases and as an assembly factor for cyclin D/Cdk6 complexes.
The work proposed here will provide insight into the fundamental regulation of the proteasome by determining the consequences of the Fbxo7 and PI31 interaction on its activity in mammalian cells.
The questions we will address include:
-Does Fbxo7 regulate proteasome activity and is this dependent on PI31? We will utilise MEFs established from Fbxo7::LacZ embryos and siRNA-mediated reduction of Fbxo7 or PI31 expression in proteasome-reporter cell lines to determine their effects on proteasome activity.
-Which proteins affect the Fbxo7-PI31 interaction? We will disrupt the ability of Fbxo7 and PI31 to form dimers using targeted mutations. We will also test whether known Fbxo7-interacting proteins can disrupt their interaction.
-Does Fbxo7 regulate PI31 in vivo? We will use a range of techniques on Fbxo7LacZ mouse-derived tissues to determine whether loss of Fbxo7 causes loss or change of localization of PI31 or a change to proteasome activity.

Planned Impact

We anticipate that our research will have a broad impact across academic, public and private arenas over both short and long time scales. The immediate beneficiaries of our work will include the other scientists in ubiquitin-proteasome research community who will receive new information on the role of Fbxo7 and PI31 in the control of proteasome function as we take the first steps into investigating their relationship in a mammalian setting. Our findings will be disseminated to the research community through the timely publication of our work and presentations at national and international conferences.

Throughout the course of the project, we expect to host under-graduate and post-graduate students who will receive training in a range of molecular, biochemical, and cell biology techniques (live cell fluorescence imaging, FACS etc), equipping them with the skills required for modern bioscience research within academic or industrial research environments. We will also regularly communicate our research and experiences within academic science with the general public at a range of different events including secondary school visits in the Cambridgeshire area and in the summer school programmes for secondary school and mature students through the Widening Participation Initiatives run by the University of Cambridge. During our current BBSRC program grant we participated in the annual Cambridge Science Festival as a forum to present our work to the general public and introduce them to some of the technologies, such as fluorescence microscopy and gene cloning using easy to understand visual and interactive aids. We intend to continue to present our work and engage the public at future science festival, and we will also take any available opportunities to communicate our findings to broader public audiences through the news media. In anticipation of these opportunities, Dr. David Nelson has already received training through the BBSRC Media Course which provided instruction and practise in the preparation of press-releases and participating in radio/TV interviews for a general audience.

Dysfunction of the proteasome, whether due to an inappropriate increase or to loss of activity has the potential to impact on many aspects of human and animal health, from age-related muscle atrophy, cancer, neurodegeneration, type II diabetes and the pathogenesis of prion-related diseases. Therefore new therapeutic drugs targeting modulators of proteasome activity have the potential to be of use to combat many diseases, especially those associated with our ageing national population. We believe that PI31 may present such a target. Only by understanding the relationship between PI31 and Fbxo7 and how it impacts on the activity of the mammalian proteasome, may we be able to best determine how to target this protein for therapeutic effect. Our discoveries may ultimately be exploited by the private sector, pharmaceutical companies which, over longer time scales (10-20 years), may be of benefit to the public and the UK healthcare system through the production of new therapeutic drugs.
 
Description The principal aim of this grant was to investigate the roles of Fbxo7 and its binding partner PI31 in the regulation of the proteasome in spermatogenesis. We extended our analysis from a single tissue type as it became apparent after creating a KO allele that the LacZ allele was hypomorphic and the homozygous mouse we were analysing and had deficiencies in multiple cell types. The overarching finding from this grant is that Fbxo7 regulates distinct, essential pathways within these different tissues. We have defined the essential functions for Fbxo7 in spermatogenesis, erythropoiesis, thymopoiesis, and neurogenesis, and found it regulates distinct pathways in each of the four cell types. However, the role of PI31 in proteasome regulation remains unclear due to conflicting reports. Our results reducing endogenous PI31 levels in human cell lines were consistent with it acting as an activator of ubiquitin-mediated proteasomal degradation. This supported previous studies on the function of PI31 orthologues in flies, plants and in yeast indicate that it is an activator of the core proteasome, regulated by hormone-dependent changes in sub-cellular localisation or by specific conditions where robust proteasome activity is required. However, in 2014, a conflicting publication reported PI31 acts as an inhibitor of 20S proteasome assembly and activity in vitro, and there is no effect on the in vitro or in vivo activity of PI31 on the 26S proteasomes. Their results suggest a lack of an effect of PI31 on overall proteasome activity, and indicate that more nuanced experiments need to be conducted. Our manuscript on Fbxo7 and PI31 in the testes is in preparation.

A consistent finding of ours is that Fbxo7 and PI31 levels correlate in all cell types tested, including the testes. However, we noted over-expression studies in cell lines showed substantial mis-localisation of PI31 throughout the cell, and therefore we discontinued approaches using non-physiological levels of expression. Consequently, goals involving experiments that required the use of over-expression of PI31 were not met. Future experiments to investigate the effect of specific point mutations will require creating mutations at the endogenous locus, perhaps with CRISPR/Cas 9 technologies. Whilst this is easiest to undertake in cell lines, given the conflicting information from using cell lines, we think experiments using animal models will be most informative.

Our studies indicate tissue-specific or stress-induced roles for Fbxo7 and PI31, and thus future studies on their functions should be carried out in specific tissues or conditions to gain insight into their specialized biology. The KO mouse did not survive weaning, and the reason for its fragility remains unknown. However, the leakiness of the Fbxo7:LacZ allele allowed sufficient expression for the mouse to survive, and it afforded us the unique opportunity to study the tissue-specific defects and the different mechanisms underlying the pathologies in each. We propose that studies with in vivo or live cell imaging will be necessary to discover the mechanisms by which Fbxo7 choses among a wide spectrum of potential substrates that we identified to regulate specific pathways within each cell type. We believe this can be approached using techniques that allow dynamic intracellular tracking of protein-protein interactions and their associated functions. Finally, studies at physiological levels will be needed to gain insight into proteasome redistribution or activity within specific tissues or under particular stress conditions. We are best positioned to undertake future studies on Fbxo7 and PI31, being experts on its biology in multiple tissue types. We believe studies to understand how a ubiquitin ligase fulfils such a diversity of functions will set a paradigm for understanding how cells are fashioned into particular shapes and how they execute specialized biological functions and ultimately how organisms are put together using a relatively small tool box of multi-purpose proteins with which to 'design' themselves.
Exploitation Route A key function of the ubiquitin-proteasome system is to rid the cell of misfolded, damaged, or aggregated proteins, and this capacity needs to be maintained over the lifespan of an organism. Damaged or misfolded proteins accumulate within cells upon stress and during normal aging. The dysfunction of the ubiquitin-proteasome system is thought to underlie certain neurological diseases, like Parkinson's disease and Alzheimer's disease. In contrast, cancer cells with their rapid cell cycles are thought to be overly reliant on higher levels of proteasome activity. Such reasoning underpins the use of drugs such as Velcade to reduce overall proteasome activity and these agents are already in use in patients. Therapeutic targeting of the proteasome either to boost or dampen its activity would clearly be of interest to pharmaceutical companies. Therefore a more detailed understanding the factors that control its activity, its constitutive and induced activity, and its prevalence in different tissue types or under stress conditions, will be important in the development of novel drugs targeting proteasomal activity.
Sectors Pharmaceuticals and Medical Biotechnology

URL https://www.laman-lab.path.cam.ac.uk/
 
Description Membership in the BBSRC Pool of Experts
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
 
Description Cambridge Cancer Centre PhD studentship
Amount £120,000 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Cambridge Cancer Centre PhD studentship
Amount £120,000 (GBP)
Organisation Cancer Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2017 
End 09/2021
 
Description Doctoral training programme
Amount £120,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2018 
End 09/2022
 
Description PhD Studentship
Amount £50,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 10/2011 
End 09/2014
 
Description PhD Studentship
Amount £110,000 (GBP)
Organisation Breast Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 01/2020
 
Description PhD Studentship
Amount £70,000 (GBP)
Organisation University of Cambridge 
Sector Academic/University
Country United Kingdom
Start 10/2013 
End 09/2017
 
Description PhD Studentship
Amount £120,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Research Training Fellowship
Sector Charity/Non Profit
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description Project grant
Amount £200,500 (GBP)
Funding ID G-1701 
Organisation Parkinson's UK 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2018 
End 05/2021
 
Description Short term travel funding
Amount £200 (GBP)
Organisation British Society for Developmental Biology 
Sector Academic/University
Country United Kingdom
Start 11/2014 
End 11/2014
 
Description Short term travel funding
Amount £390 (GBP)
Organisation University of Cambridge 
Department Clare College
Sector Academic/University
Country United Kingdom
Start 11/2014 
End 11/2014
 
Description Short term travel funding
Amount £1,570 (GBP)
Organisation European Cooperation in Science and Technology (COST) 
Sector Public
Country Belgium
Start 11/2014 
End 12/2014
 
Description Short term travel funding
Amount € 770 (EUR)
Organisation European Cooperation in Science and Technology (COST) 
Sector Public
Country Belgium
Start 09/2014 
End 09/2014
 
Description Support Grant
Amount £1,461 (GBP)
Organisation Company of Biologists 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2016 
End 05/2016
 
Title DAT-Cre Fbxo7 mice 
Description Tissue specific loss of Fbxo7. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact None 
 
Title Fbxo7 null mice 
Description We have created mice that lack expression of the Fbxo7 gene. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact None 
 
Title Fbxo7/PARK15 ES cell line 
Description ES cell lines created that have LacZ locus inserted into Fbxo7 locus. 
Type Of Material Cell line 
Provided To Others? No  
Impact None 
 
Title Fluorescent reporters of proteasome activity 
Description Fuorescent proteins (Venus, mCherry, YFP, CFP) fused in frame to ubiqutination signal 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact None 
 
Title PI31 monoclonal antibody 
Description PI31 monoclonal antibody producing hybridoma cell line 
Type Of Material Antibody 
Provided To Others? No  
Impact None 
 
Title Short hairpin targeting Fbxo7 
Description Plasmids containing short hairpins to create human cell lines with constitutive reduction in Fbxo7 expression 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact None 
 
Title Short hairpin targeting PI31 
Description Plasmids for stable integration into human cell lines to constitutively reduce the expression of PI31 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact None 
 
Title floxed Fbxo7 mice 
Description Deletion of LacZ gene flanked by LoxP site restores WT expression of Fbxo7 gene and leaves a 'floxed' allele. Mouse is now ready to be crossed to any tissue specific Cre expression mouse to create tissue specific deletions of Fbxo7 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact We have used this mouse to create two other lines, and it can be used to make tissue-specific KO mice. 
 
Title proteasome sensor cell lines 
Description Cell lines (U2OS and HEK293T) stable expressing a proteasome sensor (Venus-ubiquitin or mCherry-ubiqutin or YFP-ubiqutin or CFP-ubiquitin) 
Type Of Material Cell line 
Provided To Others? No  
Impact None 
 
Title Fbxo7 interacting proteins 
Description Mass spec of ligase used on Protoarray. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Not yet 
 
Title Fbxo7 ubiquitinated substrates 
Description Protoarray used with SCF(Fbxo7) ligase. Yielded 338 novel substrates. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact None yet 
 
Title Proteomics on Fbxo7 midbrains 
Description LC/MS on midbrain sections taken from WT and mutant Fbxo7 brains 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Data are available via ProteomeXchange with identifier PXD011666. 
URL https://www.ebi.ac.uk/pride/archive/projects/PXD011666
 
Description COST: BM1307-European network to integrate research on intracellular proteolysis pathways in health and disease (PROTEOSTASIS) 
Organisation VU University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution We are in the early stages of building a transnational translational research group, discussing strategic positioning on rare disease with an underlying defect in defective protein degradation. It is too soon to outline specific contributions.
Collaborator Contribution We are in the early stages of building a transnational translational research group, discussing strategic positioning on rare disease with an underlying defect in defective protein degradation. It is too soon to outline specific contributions.
Impact The ultimate aim is to apply for Horizon 2020 funding, but this will be a multi-disciplinary application as per the COST proposal outlines. This collaboration has attracted further funding from EMBO for a short term fellow to work in my laboratory. October to December 2015.
Start Year 2014
 
Description Nanobodies 
Organisation AstraZeneca
Department Research and Development AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We are providing cell biological systems to test the efficacy of nanobodies intracellularly.
Collaborator Contribution They make the nanobodies.
Impact This collaboration has attracted further funding from the Wellcome Trust. This is multi-disciplinary between chemistry and cell biology. This has resulted in further interest by AstraZeneca. I am acting as academic lead in their Post-doctoral training programme on producing biological Protacs.
Start Year 2013
 
Description Nanobodies 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing cell biological systems to test the efficacy of nanobodies intracellularly.
Collaborator Contribution They make the nanobodies.
Impact This collaboration has attracted further funding from the Wellcome Trust. This is multi-disciplinary between chemistry and cell biology. This has resulted in further interest by AstraZeneca. I am acting as academic lead in their Post-doctoral training programme on producing biological Protacs.
Start Year 2013
 
Description Neurodegeneration 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution We have identified a neuronal phenotype within our mouse model that resembles a neurological disorder
Collaborator Contribution Our collaborators are characterizing different aspects of the phenotype.
Impact No outputs yet. This collaboration has attracted further funding from the Rosetrees Foundation.
Start Year 2012
 
Description Post-doctoral training programme 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution I am the academic lead on a successful bid for a position in the AZ Postdoctoral training programme.
Collaborator Contribution The project will involve engineering of Protac molecules based on ubiquitin ligases.
Impact none yet
Start Year 2017
 
Description Proteasome 
Organisation Technion - Israel Institute of Technology
Country Israel 
Sector Academic/University 
PI Contribution We are expanding the capacity of the collaborator's lab, who primarily work in yeast, to do research into primary cells and tissues derived from murine models.
Collaborator Contribution Scalable proteasome assays for isolation from different tissue types.
Impact No outcomes yet. This is not multi-disciplinary.
Start Year 2013
 
Description Proteome analysis of F-box proteins 
Organisation Federal University of Sao Carlos
Department Department of Physics
Country Brazil 
Sector Academic/University 
PI Contribution We are collaborating with Dr. Felipe Teixeira on work on mechanisms of ubiquitin ligase deregulation in cancer. We are providing reagents and expertise.
Collaborator Contribution Our collaborator is undertaking proteomic screening of ubiquitin ligase and sharing datasets prior to publication. He is also applying for further funding from FAPESP.
Impact No outputs yet.
Start Year 2015
 
Title BI- OR TETRA-GUANIDINO-BIPHENYL COMPOUNDS AS SMALL MOLECULE CARRIERS 
Description That small molecules with 2 or 4 biphenyl groups mimic an alpha-helical conformation and can transport cargo into cells. 
IP Reference WO2005123676 
Protection Patent granted
Year Protection Granted
Licensed No
Impact None
 
Title Fbxo7 antibody 
Description A rabbit polyclonal antibody to Fbxo7 
IP Reference  
Protection Protection not required
Year Protection Granted
Licensed Yes
Impact None
 
Description 4th Annual UK Autophagy Network Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact I am co-organizing this annual 2-day meeting on autophagy to be held in Cambridge. It will bring researchers in the UK, Europe, and from Asia together to discuss the leading edge of research in this field.
Year(s) Of Engagement Activity 2018
URL http://autophagy.uk/2018-cambridge-meeting/
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Participation in the annual Cambridge Science Festival to tell the general public about the work ongoing in our laboratory. This year's attendance was in excess of 500 people. We also provide interactive games for young children to learn the principles of the genetic code and for older children and adults to diagnose different types of blood cancers. We produced an interactive exhibition using lasers to demonstrate fluorescence and luminescence and how we use this technology to further our work.

This is always a popular event in Cambridge, with a festival atmosphere and lots of families with children coming. Hopefully we are engaging with future scientists.
Year(s) Of Engagement Activity 2011,2012,2013,2015,2017,2018,2019
 
Description Cambridge Science Week 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Teaching two classes of Year 6 pupils at a local primary school. Presentation on the function of skin and the blood and the categories of micro-organisms that cause pathologies in humans.

no actual impacts realised to date
Year(s) Of Engagement Activity 2014
 
Description Cambridge Summer Schools 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk that sparked people's interest in pursuing a career in science at Cambridge.

This was an especially rewarding year, as I met amongst my students a young woman of Jamaican/Nigeria heritage who remembered my talk from the BAME summer programme, and she said that she particularly was inspired to apply to Cambridge because I am a scientist born in Jamaica and am now working at Cambridge. Although she is only an example of one, I am very pleased to have personally affected a young scientist in this way.
Year(s) Of Engagement Activity 2011,2012,2013,2014
 
Description Clare College Open Day 
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 150 candidate students and their families attended Clare College, to widen appreciation of who can be a scientist. I delivered a talk on cancer, which sparked a very lively question and answer session afterwards. Afterwards, I was approached by about 25 prospective students about taking the Natural Science Tripos at Cambridge.
Year(s) Of Engagement Activity 2018
 
Description Creation of Laman Laboratory web profile 
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 Created a website for our laboratory where our research is described for a lay audience, where we can list news and make our publications available to the general public.
Year(s) Of Engagement Activity 2017
URL http://www.laman-lab.path.cam.ac.uk
 
Description Discovery on Target Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact around 1000 members of the pharmaceutical industry and academic scientists attended a 4 day conference to discuss where the drug discovery practice around ubiquitin ligases.
Year(s) Of Engagement Activity 2012,2017
URL http://www.healthtech.com/Discoveryontarget_content.aspx?id=136397
 
Description International Antibody Validation Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A meeting of biosciences companies (e.g. Cell Signalling Technologies, Pfizer, Abcam) to discuss methodologies in standardizing antibody validation techniques.
Year(s) Of Engagement Activity 2016
 
Description Outreach and widening participation to schoolchildren from Hackney, London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 40 students attending mock lecture on cancer biology to get an introduction to being a student at Cambridge University. There was an extended question and answer period afterwards, and feedback to the College was very positive. Several students emailed me directly to express their thanks and appreciation for the lecture. The College has asked that I provide training to other Fellows to enable their ability to engage with school aged children.
Year(s) Of Engagement Activity 2009,2016
 
Description Science Outreach for Parkside Federation Academies 
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 Third annual Science careers day for Year 9 students with 'Speed Dating' workshop. I spoke one-to-one with approximately 30 students about the work that I do and also why and how I got into my research field.

None
Year(s) Of Engagement Activity 2013
 
Description Seminar for the Whiston Society 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Member of a four person panel debating 'Why there are so few women at the top of science.'
Year(s) Of Engagement Activity 2015