Identification and characterization of telomere proteins in Plasmodium falciparum.
Lead Research Organisation:
Keele University
Department Name: Inst for Science and Tech in Medicine
Abstract
The proposed research concerns the human malaria parasite Plasmodium. Malaria is one of the world's most debilitating infectious diseases and Plasmodium is related to several other major parasites of humans and livestock, so a better understanding of it may help us to understand and control other human and animal diseases as well. The lack of effective vaccines against most of these parasites and the emergence of drug-resistant parasites mean that there is an urgent need for research leading to new treatment strategies for malaria and related diseases.
Single-celled parasites can replicate very rapidly inside infected people or animals. One basic function that all rapidly-replicating cells must perform is the maintenance of their telomeres: the ends of the chromosomes that make up the cell's genome. Telomeres become slightly shorter every time a cell divides and will eventually become too short for survival if they are not regularly extended. Cancer cells, for example, usually develop a method for replenishing their telomeres that allows them to replicate endlessly and grow out of control, whereas most normal cells in an adult body cannot do this.
The malaria parasite, like any other single-celled organism, replenishes its telomeres every time it divides, giving it an infinite capacity for replication. However, Plasmodium is a rather unusual microbe and we know very little about the machinery that controls its telomeres. Our understanding of telomeres in human cells is quite good, but the machinery that maintains telomeres in malaria parasites does not resemble the machinery in human cells. This project therefore focuses on the maintenance of telomeres in the malaria parasite. A better understanding of this could point us in the direction of new drug targets, since disrupting the structure and maintenance of telomeres is often lethal.
To find this machinery will require a biological fishing expedition. The whole genome of the malaria parasite will be broken up into pieces and the telomeric DNA will be fished out along with the proteins bound to it. These will then be identified and the experiment will be followed up by knocking out some of these proteins in parasites grown in the lab, to test whether they actually do control telomeres.
Overall, the study will give us a better understanding of the mechanisms that maintain the telomeres of these unusual parasites. It may inform new drug strategies to combat malaria and related parasitic diseases affecting both humans and animals. The outcomes of the research will be published in open-access scientific journals and presented at international conferences. They will be communicated to the general public via lay summaries on appropriate websites and via science-writing in magazines and/or online.
Single-celled parasites can replicate very rapidly inside infected people or animals. One basic function that all rapidly-replicating cells must perform is the maintenance of their telomeres: the ends of the chromosomes that make up the cell's genome. Telomeres become slightly shorter every time a cell divides and will eventually become too short for survival if they are not regularly extended. Cancer cells, for example, usually develop a method for replenishing their telomeres that allows them to replicate endlessly and grow out of control, whereas most normal cells in an adult body cannot do this.
The malaria parasite, like any other single-celled organism, replenishes its telomeres every time it divides, giving it an infinite capacity for replication. However, Plasmodium is a rather unusual microbe and we know very little about the machinery that controls its telomeres. Our understanding of telomeres in human cells is quite good, but the machinery that maintains telomeres in malaria parasites does not resemble the machinery in human cells. This project therefore focuses on the maintenance of telomeres in the malaria parasite. A better understanding of this could point us in the direction of new drug targets, since disrupting the structure and maintenance of telomeres is often lethal.
To find this machinery will require a biological fishing expedition. The whole genome of the malaria parasite will be broken up into pieces and the telomeric DNA will be fished out along with the proteins bound to it. These will then be identified and the experiment will be followed up by knocking out some of these proteins in parasites grown in the lab, to test whether they actually do control telomeres.
Overall, the study will give us a better understanding of the mechanisms that maintain the telomeres of these unusual parasites. It may inform new drug strategies to combat malaria and related parasitic diseases affecting both humans and animals. The outcomes of the research will be published in open-access scientific journals and presented at international conferences. They will be communicated to the general public via lay summaries on appropriate websites and via science-writing in magazines and/or online.
Technical Summary
The proposed work will identify and characterise novel telomere-associated proteins in the protozoan parasite Plasmodium falciparum. This parasite (along with other apicomplexans of medical and veterinary importance: Toxoplasma, Cryptosporidium, Eimeria, Babesia and Theileria) belongs to an early-branching, highly-divergent lineage and few of the factors that cap, regulate and maintain its telomeres have been identified by homology with model organisms. Telomere maintenance is, however, a vital basic function, and may also represent a novel drug target.
This project will use Proteomics of Isolated Chromatin Segments (PICh) to identify the protein complement of telomeric DNA from P. falciparum. The PICh technique, in which cross-linked protein-DNA complexes are isolated via a specific DNA probe before identifying the proteins by mass spectrometry, was recently very successful in identifying known and novel components of the human telomere-binding complex.
After identifying the telomeric proteome in wildtype P. falciparum, telomeric proteins in sirtuin-knockout parasites will be identified for comparison. The two 'sirtuin' histone deacetylases play key roles in regulating expression of sub-telomeric virulence genes. I have shown that they also affect telomere length and genome stability, so these enzymes may be central components of a telomere-regulating complex.
Telomeric proteins of particular interest will be validated by immunofluorescence with fluorescence in situ hybridisation, to verify their specificity for the telomere. Genetic knockouts will then be generated and phenotyped for an initial characterisation of the roles of these proteins: telomere length and telomere stability in knockout lines will be analysed by Southern blotting and karyotyping.
The project will improve our understanding of a fundamental aspect of Plasmodium biology, as well as opening up new avenues for research on Plasmodium and other important apicomplexan parasites.
This project will use Proteomics of Isolated Chromatin Segments (PICh) to identify the protein complement of telomeric DNA from P. falciparum. The PICh technique, in which cross-linked protein-DNA complexes are isolated via a specific DNA probe before identifying the proteins by mass spectrometry, was recently very successful in identifying known and novel components of the human telomere-binding complex.
After identifying the telomeric proteome in wildtype P. falciparum, telomeric proteins in sirtuin-knockout parasites will be identified for comparison. The two 'sirtuin' histone deacetylases play key roles in regulating expression of sub-telomeric virulence genes. I have shown that they also affect telomere length and genome stability, so these enzymes may be central components of a telomere-regulating complex.
Telomeric proteins of particular interest will be validated by immunofluorescence with fluorescence in situ hybridisation, to verify their specificity for the telomere. Genetic knockouts will then be generated and phenotyped for an initial characterisation of the roles of these proteins: telomere length and telomere stability in knockout lines will be analysed by Southern blotting and karyotyping.
The project will improve our understanding of a fundamental aspect of Plasmodium biology, as well as opening up new avenues for research on Plasmodium and other important apicomplexan parasites.
Planned Impact
Most research on infectious pathogens ultimately aims to inform or develop new therapeutics or control strategies, and thus to benefit affected communities. The project proposed here is no exception, since apicomplexan parasites have a severe impact on both human and animal health within the UK and across the world. In the case of malaria, caused by Plasmodium, the affected communities include human populations in the tropics and sub-tropics (almost 250 million cases of disease and 1 million deaths per year) as well as travellers, from tourists to military personnel, who visit malaria-endemic regions. The burden of disease and the socio-economic impact are clearly huge and there is an urgent need for a better understanding of the parasite to inform new control strategies. Besides Plasmodium, the related parasites Toxoplasma and Cryptosporidium cause significant human disease in immuno-compromised individuals, while Babesia, Theileria and Eimeria are major parasites of cattle and poultry.
Basic biological studies, leading through to applied research, have the potential to reveal new drug targets for these pathogens. Telomere-associated proteins represent a particularly promising target because a rapidly-replicating protozoan parasite must maintain its telomeres to survive, and the proposed project aims to identify exactly such targets. Newly discovered proteins usually take some years to translate to the clinic as drug targets, but there are many examples of basic research generating targets that soon move into drug screening studies. New drugs to combat apicomplexan parasites could ultimately benefit diverse groups of people in the UK and the wider world, including residents of malaria-endemic countries, travellers, military personnel and those in the agricultural industry.
The impact of this project will extend beyond the long-term possibility of discovering new anti-parasitic drugs. Supporting more malaria researchers will expand the community working on this important disease, thus raising awareness and facilitating more research funding. My continuing career as a parasite biologist depends upon early-career grants such as this one and I hope that my career will ultimately include both basic research and field studies, as my postdoctoral work did. Field studies can bring many particular benefits to the communities affected by the malaria parasite - by bringing people into contact with educated researchers as well as by providing employment and direct scientific education. For example, while working in the Gambia, I had many conversations with Gambian citizens on public transport about the importance of completing courses of malaria treatment, treating young children promptly before severe disease develops and using bednets, amongst other issues. The value of such contact in educating local communities and raising the profile of UK-funded researchers should not be underestimated.
Turning to impacts within the UK, my career will include undergraduate and postgraduate teaching as well as research, and it is particularly incumbent upon scientists studying neglected and tropical parasites to raise their profile and enthuse students about working on important public health topics that can remain 'invisible' in the developed world. I hope to inspire a new generation of students to consider careers in biological research, in international development, or in human or veterinary medicine - all of which will benefit both the students themselves and the communities affected by parasitic diseases.
Finally, I am employed at Keele University in North Staffordshire, an area of high unemployment that was recently designated by the government for a Local Enterprise Partnership to promote economic redevelopment. The proposed project will immediately bring skilled academic work to a region with few such opportunities in which the university is a significant and valuable employer.
Basic biological studies, leading through to applied research, have the potential to reveal new drug targets for these pathogens. Telomere-associated proteins represent a particularly promising target because a rapidly-replicating protozoan parasite must maintain its telomeres to survive, and the proposed project aims to identify exactly such targets. Newly discovered proteins usually take some years to translate to the clinic as drug targets, but there are many examples of basic research generating targets that soon move into drug screening studies. New drugs to combat apicomplexan parasites could ultimately benefit diverse groups of people in the UK and the wider world, including residents of malaria-endemic countries, travellers, military personnel and those in the agricultural industry.
The impact of this project will extend beyond the long-term possibility of discovering new anti-parasitic drugs. Supporting more malaria researchers will expand the community working on this important disease, thus raising awareness and facilitating more research funding. My continuing career as a parasite biologist depends upon early-career grants such as this one and I hope that my career will ultimately include both basic research and field studies, as my postdoctoral work did. Field studies can bring many particular benefits to the communities affected by the malaria parasite - by bringing people into contact with educated researchers as well as by providing employment and direct scientific education. For example, while working in the Gambia, I had many conversations with Gambian citizens on public transport about the importance of completing courses of malaria treatment, treating young children promptly before severe disease develops and using bednets, amongst other issues. The value of such contact in educating local communities and raising the profile of UK-funded researchers should not be underestimated.
Turning to impacts within the UK, my career will include undergraduate and postgraduate teaching as well as research, and it is particularly incumbent upon scientists studying neglected and tropical parasites to raise their profile and enthuse students about working on important public health topics that can remain 'invisible' in the developed world. I hope to inspire a new generation of students to consider careers in biological research, in international development, or in human or veterinary medicine - all of which will benefit both the students themselves and the communities affected by parasitic diseases.
Finally, I am employed at Keele University in North Staffordshire, an area of high unemployment that was recently designated by the government for a Local Enterprise Partnership to promote economic redevelopment. The proposed project will immediately bring skilled academic work to a region with few such opportunities in which the university is a significant and valuable employer.
Organisations
- Keele University (Lead Research Organisation)
- Heidelberg University (Collaboration)
- University of Lisbon (Collaboration)
- Boston Children's Hospital (Collaboration)
- UNIVERSITY OF PRETORIA (Collaboration)
- Food and Drug Administration (FDA) (Collaboration)
- Lohengrin (Institut Laue-Langevin) (Collaboration)
- Radboud University Nijmegen (Collaboration)
- The Wellcome Trust Sanger Institute (Collaboration)
- UNIVERSITY OF LIVERPOOL (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- University of Würzburg (Collaboration)
People |
ORCID iD |
Catherine Merrick (Principal Investigator) |
Publications
Edwards-Smallbone J
(2016)
A candidate Plasmodium falciparum telomere-binding protein expressed in gametocytes (poster presentation)
Edwards-Smallbone J
(2021)
Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA
Edwards-Smallbone J
(2022)
Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA
in Frontiers in Cellular and Infection Microbiology
Edwards-Smallbone J
(2022)
Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA.
Edwards-Smallbone J
(2022)
Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA
Edwards-Smallbone, J
(2019)
A novel putative telomere-binding protein in Plasmodium falciparum (poster presentation, MPM 2019)
Merrick CJ
(2015)
Transfection with thymidine kinase permits bromodeoxyuridine labelling of DNA replication in the human malaria parasite Plasmodium falciparum.
in Malaria journal
Stanojcic S
(2017)
Single-molecule analysis reveals that DNA replication dynamics vary across the course of schizogony in the malaria parasite Plasmodium falciparum.
in Scientific reports
Description | 1) A comprehensive bioinformatic search and cataloging of candidate telomere-binding proteins was conducted in Plasmodium. 2) Considerable efforts were made to develop the PiCh methodology for Plasmodium parasites, in order to indentify novel telomere-binding proteins agnostically. Many technical hurdles were encountered (low and non-specific sample yields; contaminating proteins from erythrocytes and other sources in the MassSpec results, insufficient sensitivity in MassSpec instrumentation available at Keele; construction work occuring at Keele that put the MassSpec lab out of action for long periods, etc.). These were, in general, overcome and the final round of PiCh samples, produced shortly before the grant ended, yielded one potential protein of interest (PfGBP2). This was identified via Mass Spec with a new collaborative partner at Liverpool University. Time limitations prevented futher work on PfGBP2 during the period of the grant, but followup work proceeded independently in 2018-2020. A manuscript on this protein was prepared within 2019 (including the PiCh methods-development work as well) and the data were presented on a poster in late 2019 (MPM2019, Massachusetts). A final experiment for this paper (ChIP-seq on the candidate protein) was underway when the pandemic shutdown occurred in 2020, delaying the expected submission of our manuscript, which was finally submitted in mid 2021. Unfortunately, in Dec 2020 another paper on PfGBP2 had been published by a competitor lab, with parts of the data being almost identical to those in our own manuscript. We therefore expanded the unique parts of our own work prior to submission, and we anticipate a lower-impact publication within 2021. 3) Alongside the PiCh work, a large amount of molecular-genetic work was conducted on the telomere-binding candidate protein PfTRF1. This target proved refractory to many modes of genetic intervention; the results from this work were nonetheless written up for publication, but, being largely 'negative', they proved difficult to publish in journals including Malaria Journal and Plos One. A volunteer in the lab pursued further work on TRF1 in 2017-18, and we still hope to construct a viable publication from this considerable body of work. 4) Finally, a side project developed alongside this work, by the PI Dr Merrick, to monitor DNA replication in Plasmodium parasites, was very successful. It resulted in preliminary data contributing to two successful awards of MRC and ERC grants within 2016, and two publications (Merrick, Malar J. 2015 and Stanojcic et al., Scientific Reports 2017). |
Exploitation Route | The PiCh method may be applicable to other regions in the Plasmodium genome. The DNA-replication-labelling methodology has already elicited much interest from several other groups in the field and will be widely applicable in drug studies, cell-cycle studies, etc. |
Sectors | Pharmaceuticals and Medical Biotechnology |
URL | https://www.biorxiv.org/content/10.1101/2021.07.02.450898v1 |
Description | In parallel with his research work, the PDRA on this grant, Dr James Edwards-Smallbone, developed a highly successful outreach activity that was was used by himself and others at Keele, and continues to be used now that the award has finished. The activity, 'Hector the Vector' has been used at University Community Day, Science-week events and outreach to school groups of various ages. It will be included in a package of resources to be posted on the website of the British Society for Parasitology. |
Sector | Education |
Impact Types | Cultural Societal |
Description | ERC Consolidator Grants |
Amount | € 1,998,696 (EUR) |
Funding ID | PlasmoCycle |
Organisation | European Research Council (ERC) |
Sector | Public |
Country | Belgium |
Start | 05/2017 |
End | 05/2022 |
Description | Faculty Research Support Fund |
Amount | £707 (GBP) |
Organisation | Keele University |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2016 |
End | 01/2016 |
Title | BrdU labelling of DNA replication in Plasmodium parasites |
Description | The labelling of DNA replication with bromo-/iodo-/chloro-deoxyuridine (BrdU/IdU/CldU), has long been a workhorse assay in human cell-cycle studies, identifying cells that are in S-phase swiftly and sensitively. However, this was not previously possible in Plasmodium - despite conflicting reports in the literature going back 25 years - because the parasite relies only on de novo synthesis of pyrimidines and does not salvage thymidine analogues like BrdU for conversion into nucleotides. I have recently showed that expressing a TK enzyme in transgenic parasites supplies the pyrimidine salvage pathway and allow parasites to be labelled with BrdU (see paper by Merrick, Malar J. 2015). Therefore, this can now be exploited to investigate how DNA replication is organised, from the whole-cell to the single-molecule level, during both schizogony and gametogenesis. |
Type Of Material | Technology assay or reagent |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | I am actively exploiting this method to study replication dynamics in Plasmodium. I have two major grants under assessment (BBSRC and ERC) based on the technique, and I have shared it with other groups, at least one of whom is actively using it to answer related questions in Plasmodium biology. |
URL | https://malariajournal.biomedcentral.com/articles/10.1186/s12936-015-1014-7 |
Title | DNA combing in P. falciparum |
Description | Part of an ongoing project to develop DNA replication labelling in Plasmodium parasites, which was developed by Dr Merrick as a side-project from the referenced grants. See also the methodology paper Merrick, Malar J. 2015. This collaborative work with the Sterkers lab at Montpellier University has, for the first time, developed DNA combing and DNA fibre analysis for Plasmodium. See paper currently under review at Scientific Reports: 'Single-molecule Analysis Reveals that DNA Replication Dynamics Vary Across the Course of Schizogony in the Malaria Parasite Plasmodium falciparum.' Slavica Stanojcic, Nada Kuk, Imran Ullah, Yvon Sterkers, Catherine J. Merrick. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Paper on this technique is still under review. Once published, we anticipate wider uptake, as has already occurred with the preceding methods paper (Merrick, Malar J. 2015.) which has prompted several requests for collaborative work. This methodology was a key contributor to a successful ERC grant awarded to Dr Merrick in 2016. |
Description | ChIP for PfGBP2 in P. falciparum parasites, Radboud University |
Organisation | Radboud University Nijmegen |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | A candidate P. falciparum telosome protein, PfGBP2, identified in this project, was epitope-tagged, subjected to chromatin immunoprecipitation, and sent to collaborators Dr Bartfai and coworkers at Radboud University. |
Collaborator Contribution | Dr Bartfai's group conducted and the GBP2 ChIP-seq and analysed resultant data. |
Impact | After considerable optimisation and repeats, we concluded that GBP2 is not amenable to ChIP. This conflicts with a publication that appeared in Dec 2020 from a competitor lab, reporting ChIP of GBP2 with the same methodology. However, poor reporting standards in this paper make it impossible to verify or reanalyse their results. Our data are still destined for a paper on PfGBP2 (which in late 2019 was already complete except for the ChIP data, and was scheduled for submission in early 2020 - considerably delayed by the pandemic shutdown, and then by the competing publication, which now necessitates some re-writing). Our work will be submitted within 2021. |
Start Year | 2019 |
Description | DNA combing, Montpellier University |
Organisation | University of Wurzburg |
Department | Parasitology |
Country | Germany |
Sector | Academic/University |
PI Contribution | I conducted method-development in preparing Plasmodium for DNA combing, and provided parasite material to collaborators in Montpellier. |
Collaborator Contribution | The collaborators provide access to the DNA combing facility, and data analysis skills for the resultant DNA fibre images. |
Impact | Preliminary data in support of two major grant applications (BBSRC and ERC); the ERC application being successful in 2017. Publication in the journal Scientific Reports, 2017. |
Start Year | 2016 |
Description | Development of BrdU-incorporation methodology in Plasmodium berghei & Plasmodium knowlesi |
Organisation | Imperial College London |
Department | VIGILab |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Technical advice & discussion concerning BrdU-labelling methodology for development of TK-expressing P. berghei at ICL; technical advice & plasmid provided for development of TK-expressing P. knowlesi at Sanger. |
Collaborator Contribution | A researcher in the Vigilab developed a TK-expressing P. berghei which they are now characterising. At WT Sanger, existing collaborators in the Rayner lab have developed a TK P. knowlesi line. My lab now has both these lines to be taken forward in a compartive study of replication across 3 species of Plasmodium. |
Impact | Prelim data showing the BrdU incorporation is feasible in TK-expressing P. berghei (presented at MAM 2015 conference) & also in TK-expressing P. knowlesi. |
Start Year | 2015 |
Description | Development of BrdU-incorporation methodology in Plasmodium berghei & Plasmodium knowlesi |
Organisation | The Wellcome Trust Sanger Institute |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Technical advice & discussion concerning BrdU-labelling methodology for development of TK-expressing P. berghei at ICL; technical advice & plasmid provided for development of TK-expressing P. knowlesi at Sanger. |
Collaborator Contribution | A researcher in the Vigilab developed a TK-expressing P. berghei which they are now characterising. At WT Sanger, existing collaborators in the Rayner lab have developed a TK P. knowlesi line. My lab now has both these lines to be taken forward in a compartive study of replication across 3 species of Plasmodium. |
Impact | Prelim data showing the BrdU incorporation is feasible in TK-expressing P. berghei (presented at MAM 2015 conference) & also in TK-expressing P. knowlesi. |
Start Year | 2015 |
Description | Drug mode-of-action analysis via BrdU-incorporation into P. falciparum parasites |
Organisation | Heidelberg University |
Department | Centre for Infectious Diseases, Parasitology |
Country | Germany |
Sector | Academic/University |
PI Contribution | TK-expressing parasite lines that incorporate BrdU to monitor DNA replication; reagents, methodology & hosting of visiting researchers |
Collaborator Contribution | Since publication of this new method (Merrick, Malar J 2015) several research groups have approached me wishing to use the technique. The Lanzer and Birkholtz group have provided/will provide antimalarial drugs to test, plus visiting researchers. |
Impact | Prelim data on the mode of action of 1 candidate antimalarial in blocking DNA replication (data generated by visiting researcher from Heidelberg to Keele). |
Start Year | 2016 |
Description | Drug mode-of-action analysis via BrdU-incorporation into P. falciparum parasites |
Organisation | University of Pretoria |
Country | South Africa |
Sector | Academic/University |
PI Contribution | TK-expressing parasite lines that incorporate BrdU to monitor DNA replication; reagents, methodology & hosting of visiting researchers |
Collaborator Contribution | Since publication of this new method (Merrick, Malar J 2015) several research groups have approached me wishing to use the technique. The Lanzer and Birkholtz group have provided/will provide antimalarial drugs to test, plus visiting researchers. |
Impact | Prelim data on the mode of action of 1 candidate antimalarial in blocking DNA replication (data generated by visiting researcher from Heidelberg to Keele). |
Start Year | 2016 |
Description | GBP2 with Painter lab, US FDA |
Organisation | Food and Drug Administration (FDA) |
Country | United States |
Sector | Public |
PI Contribution | Dr Painter's lab is interested in RNA binding proteins and has identified PfGBP2 independently from us, as an RNA binding protein. This was reported at the 2021 MPM meeting (virtual). Following discussion at this conference, we supplied a GBP2 recombinant protein expression construct and a parasite line expressing tagged GBP2 (both published in our paper on GBP2 in 2022) to further Dr Painter's investigations. |
Collaborator Contribution | Dr Painter plans to use our materials to further her investigation of PfGBP2. |
Impact | No outputs yet. |
Start Year | 2021 |
Description | Investigation of basic parasite biology via BrdU-incorporation into P. falciparum parasites |
Organisation | Boston Children's Hospital |
Country | United States |
Sector | Hospitals |
PI Contribution | TK-expressing parasite lines that incorporate BrdU to monitor DNA replication; reagents & methodology for this work. |
Collaborator Contribution | Since publication of this new method (Merrick, Malar J 2015) several research groups have approached me wishing to use the technique. The Dvorin and Mota groups have expressed interest in sharing the technology to investigate their various phenotypes of interest in Plasmodium biology (genetic mutants etc.): work is ongoing or in development. |
Impact | None yet |
Start Year | 2018 |
Description | Investigation of basic parasite biology via BrdU-incorporation into P. falciparum parasites |
Organisation | University of Lisbon |
Country | Portugal |
Sector | Academic/University |
PI Contribution | TK-expressing parasite lines that incorporate BrdU to monitor DNA replication; reagents & methodology for this work. |
Collaborator Contribution | Since publication of this new method (Merrick, Malar J 2015) several research groups have approached me wishing to use the technique. The Dvorin and Mota groups have expressed interest in sharing the technology to investigate their various phenotypes of interest in Plasmodium biology (genetic mutants etc.): work is ongoing or in development. |
Impact | None yet |
Start Year | 2018 |
Description | Mass Spectrometry on Plasmodium telomere PiCh samples, Liverpool Centre for Proteome Research |
Organisation | University of Liverpool |
Department | Centre for Proteome Research |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided samples for Mass Spectrometry: Plasmodium telosome samples isolated by PiCh |
Collaborator Contribution | Provided Mass Spectrometry service & analysis |
Impact | A publication including this M/S data has been drafted, including follow-up work on one of the protein candidates identified. This work was started in 2018 and remains underway. |
Start Year | 2016 |
Description | Protein structural studies on PfTRF1 |
Organisation | Lohengrin (Institut Laue-Langevin) |
Country | France |
Sector | Academic/University |
PI Contribution | The research concept, protein expression constructs and preliminary work were provided by my team. |
Collaborator Contribution | The lab of Prof Trevor Forsyth provided large-scale expression facilities and will provide access to crystalisation screening |
Impact | Expression and purification methodology for PfTRF1 was developed, but crystalisation studies could not ultimately be conducted due to technical problems with the protein. |
Start Year | 2015 |
Description | 'Hector the Vector' at Keele Community Day's Science Roadshow, 2014 and 2015 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | The game was tremendously popular, sparked many questions about tropical disease research at Keele, and has since been used by Dr Edwards-Smallbone at other school visits to Keele. |
Year(s) Of Engagement Activity | 2014,2015 |
URL | http://www.keele.ac.uk/lifesci/newsandevents/2014/communityday.php |
Description | 'Women in Science' schools visit to Keele, 2014 and 2015 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Highly positive feedback from students and school teachers involved 'It has been an absolutely brilliant day, with a really good blend of theory and practical activity. It was an excellent opportunity for our young people to engage with academics and so many Keele students.' - Paul Winterburn, Biddulph High School teacher. 'I am 100% coming to Uni now, man...' - Year-9 pupil. |
Year(s) Of Engagement Activity | 2014,2015 |
URL | http://www.keele.ac.uk/lifesci/newsandevents/2014/womeninscience.php |
Description | Article in Slightly Foxed Magazine |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Article 'A Scientist for all Seasons' (A review of E.O Wilson's 'Biophilia') Merrick, C.J. Slightly Foxed, Summer 2014 issue. Published as part of an occasional series reviewing classic books in the scientific literature, for a literary magazine with a circulation of ~7000. |
Year(s) Of Engagement Activity | 2014 |
URL | https://foxedquarterly.com/Slightly-Foxed-Issue-42-Catherine-Merrick-on-Biophilia/ |
Description | BSP YouTube channel |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | PI Catherine Merrick became Hon. Communications Secretary for the British Society of Parasitology in 2015. As part of this job she has set up a YouTube channel to host videos about the society, as well as curating the society's webpage (receiving ~200 hits per day) and Facebook and Twitter groups (almost 2000 members). Collectively, this BSP activity provides up-to-date and accessible news and information on parasitology to a very broad sector of the public. |
Year(s) Of Engagement Activity | 2015 |
URL | https://www.youtube.com/channel/UCo46EvqlMbWmgABiM1cBfdA |
Description | BSP social media |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | PI Catherine Merrick became Hon. Communications Secretary for the British Society of Parasitology in 2015. As part of this job she curates the society's fast-growing Facebook and Twitter groups (which have approximately doubled in membership during her tenure and now have almost 3000 members). https://www.facebook.com/groups/8573726067/ and https://twitter.com/BSPparasitology. They provide up-to-date and accessible news and information on parasitology to a broad sector of the public: in the case of the Twitter group, primarily parasitology researchers; in the Facebook group, a large cohort of interested parties and practitioners in developing countries. |
Year(s) Of Engagement Activity | 2015,2016,2017 |
URL | https://twitter.com/BSPparasitology |
Description | Big Biology Day at Staffordshire University |
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 | The 'Big Biology Day' was put on by staff from Keele and Staffs Uni as a large spectrum of stalls and events to inspire public interest in biology as part of ther Royal Society for Biology's "Biology Week". PCRA Dr James Edwards-Smallbone contributed the 'Hector the Vector' activity. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.rsb.org.uk/get-involved/biologyweek/big-biology-days |
Description | Bugbitten blog, C Merrick 2014 |
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 | These blog entries, highlighting important papers in the parasitology/vector biology literature, regularly receive over 1000 hits. |
Year(s) Of Engagement Activity | 2014 |
URL | http://blogs.biomedcentral.com/bugbitten/2014/04/01/throwing-the-switch-gametocytogenesis-in-malaria... |
Description | Bugbitten blog, C Merrick 2015 |
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 | These blog entries, highlighting important papers in the parasitology/vector biology literature, regularly receive over 1000 hits. |
Year(s) Of Engagement Activity | 2015 |
URL | http://blogs.biomedcentral.com/bugbitten/2015/08/21/rinse-and-repeat-can-mosquito-passage-reset-mala... |
Description | Bugbitten blog, J Edwards Smallbone 2014 |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | Yes |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | These blog entries, highlighting important papers in the parasitology/vector biology literature, regularly receive over 1000 hits. Dr James Edwards-Smallbone, who led on this blog entry, has agreed to write further occasional blogs |
Year(s) Of Engagement Activity | 2014 |
URL | http://blogs.biomedcentral.com/bugbitten/2014/08/11/taking-turns-how-plasmodium-changes-its-spots/ |
Description | New BSP website |
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 | In her role as Hon. Communications Secretary for the British Society for Parasitology, PI Dr Catherine Merrick has had a new website for the British Society of Parasitology commissioned, built and gone-live in autumn 2016. The website includes a much-expanded public engagement section. |
Year(s) Of Engagement Activity | 2016 |
URL | http://bsp.uk.net/ |
Description | School visit, Madeley High School |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Keele staff including PI Catherine Merrick visited a local school to talk about their careers as female scientists and to run hands-on workshops for GCSE-level pupils. |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.keele.ac.uk/lifesci/newsandevents/2015/intwomensday.php |
Description | School visit, Malbank School |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | An evening talk on malaria for students and their parents as part of an extension programme at a local school |
Year(s) Of Engagement Activity | 2015 |
Description | School visit, South Cheshire College |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Visit to give a talk on malaria and on university entry at a local sixth form college |
Year(s) Of Engagement Activity | 2015 |
URL | http://www.keele.ac.uk/lifesci/newsandevents/2015/scheshirecollege.php |
Description | School visit, Walsall College |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Visit to give a talk on malaria and on university entry at a regional sixth form college |
Year(s) Of Engagement Activity | 2014 |
Description | Talk at Stoke on Trent college |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | A talk by PI Dr Merrick to 6th formers in the Stoke on Trent college university extension programme, to encourage interest in biology & applications to university |
Year(s) Of Engagement Activity | 2016 |
Description | Talk by JES in BSP Meeting Public Engagement session |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | PDRA Dr James Edwards-Smallbone gave a talk about his successful outreach activities ('Hector the Vector' and others) in the session on Public Engagement at the 2016 BSP Spring Meeting in London. PI Dr Merrick chaired this session. |
Year(s) Of Engagement Activity | 2016 |
Description | Wikithon |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | PI Catherine Merrick attended a Wikipedia edit-a-thon at the Royal Society in London. The event, organised by Wikimedia UK, the Medical Research Council (MRC) and the Royal Society, aimed to improve the coverage of eminent female scientists on Wikipedia. During the day, more than a dozen new Wikipedia pages were created for female Fellows of the Royal Society in disciplines from Molecular Biology to Tropical Medicine to Physical Chemistry. Dr Merrick contrubuted a page on Professor Janet Hemingway. |
Year(s) Of Engagement Activity | 2013 |
URL | https://en.wikipedia.org/wiki/Janet_Hemingway |