The Tick Cell Biobank - a UK and international biological resource

Lead Research Organisation: University of Liverpool
Department Name: Institute of Infection and Global Health

Abstract

Ticks are bloodfeeding arthropods which, as well as causing direct damage to their hosts, transmit many diseases of livestock, companion animals and humans. Research into prevention and cure of these diseases, caused by viruses, bacteria, protozoa and filarial worms, is greatly assisted by the use of cell culture systems to study both how tick cells function, and how and why they transmit disease-causing pathogens. Such culture systems, called cell lines, have been developed for many disease-carrying ticks, but they require special skills and much time and patience to establish and maintain. Seven years ago a central collection, the Tick Cell Biobank (TCB), was created for all the tick cell lines available now and in future. The TCB distributes tick cell lines (TCL) on request to research scientists all over the world and provides essential training in their maintenance. The TCB also carries out characterisation studies on TCL, as very little is known about most of them, and is creating new cell lines from species of ticks not already represented in the collection. This proposal requests funding to secure the long-term future of the TCB as an essential resource underpinning UK and international tick and tick-borne disease research, to expand the resource to include cell lines derived from other important arthropods such as biting midges, mites and honeybees, and to give added value to the cell lines through characterisation, cloning and genome sequencing, thereby ensuring that these unique and invaluable biological resources continue to be available to the scientists who need to use them in biomedical, veterinary and agricultural research.

Since the TCB was established in 2009, the crucial role played by TCL in research into ticks and the diseases they transmit has become increasingly clear. Indeed, interest in TCL and the methods used to generate them has spread to encompass pathogens transmitted by other arthropods such as mites, fleas and lice. With environmental and climate change driving the emergence of new vector-borne diseases, the demand for cell lines derived from ticks and other arthropods is likely to continue to increase in the future. This proposal includes generation of novel cell lines from ticks, mites and insects such as sand flies and midges both in-house and through dissemination of the required expertise to scientists in laboratories specialising in these arthropods.

Establishment of TCL takes many years and requires specialised expertise, much patience and, importantly, a stable background of laboratory support. The TCB has brought together almost all the TCL available worldwide into a single repository and point of contact for supply of TCL and training in their maintenance (essential for successful transfer of TCL to recipient laboratories). The TCB has been enormously successful over the past 7 years, generating 18 new TCL, supplying TCL to 71 recipient laboratories and training 80 young scientists representing 27 countries in Europe, Asia, Africa, North and South America. This proposal includes a workpackage specifically aimed at raising the profile of, and improving access to, TCL and training in lower and middle-income countries, by establishing outposts of the TCB in Malaysia, Kenya and Brazil.

TCL from the TCB have already facilitated a wide range of studies, but much remains to be done. UK and global research has only scratched the surface of knowledge of these economically important and biologically fascinating parasites, their microbiota and the pathogens they transmit. Continued maintenance and expansion of the unique resource represented by the TCB, including genomic and molecular characterisation of TCL and generation of new arthropod cell lines, is essential to support this research now and for many years to come.

Technical Summary

Tick cell lines (TCL) are valuable research tools that are increasingly applied in many areas of laboratory-based study of tick biology and control, and the viral, bacterial and protozoan pathogens that ticks transmit, as well as the endogenous microorganisms that they harbour. The Tick Cell Biobank (TCB) is a repository for continuous TCL, which are maintained both as growing cultures and, where possible, as cryopreserved stabilates. As well as housing almost all the TCL currently available worldwide, the TCB provides training in establishment and maintenance of TCL to recipient scientists and generates novel cell lines from additional species of ticks and other arthropod vectors. As such, the TCB is a unique biological resources not just in the UK but also globally. The TCB houses TCL derived from embryos, larvae and/or nymphs of 15 ixodid and two argasid tick species and one biting midge, a small collection of BSL2 tick-borne bacteria, and cell lines are under development from seven additional tick species or geographical strains and one sand fly species. We propose, by establishing the TCB at the University of Liverpool, to secure its long-term future as an essential resource underpinning UK and international research into ticks, tick-borne diseases and other arthropod vectors. Moreover, we will give added value to selected TCL by genome sequencing, phenotype characterisation and cloning, thereby enhancing their uptake and application in a wide range of research areas including tick-pathogen interactions, tick innate immunity, tick functional genomics, proteomics and interactomics, and tick and disease control based on acaricides and vaccines against tick and pathogens. Through a GCRF-funded workpackage, we will establish outposts of the TCB in Malaysia, Kenya and Brazil, thereby facilitating uptake of TCL and associated technology in these and neighbouring lower- and middle-income countries.

Planned Impact

In addition to the academic beneficiaries listed in the previous section, the following groups should benefit from the Tick Cell Biobank as a UK and international biological resource in the short term:

- The Institute for Infection and Global Health, other departments of the University of Liverpool, and other nearby institutes such as the Liverpool School of Tropical Medicine and universities on the region will gain opportunities for enhanced research collaborations and training opportunities for students.
- Links between the LMIC institutes involved in the GCRF workpackage and University of Liverpool will be created and strengthened, facilitating future collaborations
- The profile of the UK Bioscience contribution to addressing and solving problems caused by ticks and tick-borne pathogens worldwide, in both veterinary and human medicine, will be raised

In the longer term, use of tick cell lines by UK and international researchers will facilitate delivery of i) improved tick control methods using novel acaricides, plant-based products and anti-tick vaccines, and ii) improved detection, diagnosis, treatment and control of tick-borne pathogens based on pathogens propagated in tick cell lines. These will benefit the following groups:

- Veterinarians who will have access to improved products for diagnosis, treatment and control of ticks and tick-borne diseases affecting livestock and companion animals in the UK and other countries
- Clinicians who will similarly have access to increased knowledge of tick-borne diseases affecting humans and to improved products for diagnosis and treatment of tick-borne diseases affecting humans in the UK and other countries
- Large- and small-scale livestock farmers in the UK and other developed countries whose livestock will be healthier and more productive, thereby increasing their income from sale of animals and animal products, and decreasing their costs for tick and disease control. This will contribute to improved UK food security.
- Through the outputs of collaborative research springboarded by both the parent Tick Cell Biobank and the outposts established through the GCRF workpackage, LMIC farmers and smallholders who will have access to more effective and affordable tick control methods to reduce or eliminate tick burdens on their livestock, and more effective, accessible and affordable vaccines and/or treatments for the tick-borne diseases affecting their livestock. This will in turn improve the access of poor farmers and smallholders, their families and consumers in the general population in LMIC to more and better quality sources of animal protein in their diets

Novel cell lines developed from other arthropod groups such as mites, sand flies, midges, lice, fleas and plant pests, and expertise in their establishment disseminated by the Tick Cell Biobank will additionally benefit equivalent groups affected by these arthropod vectors and the pathogens that they transmit, in ways similar to those outlined above.

Publications

10 25 50

 
Description The Tick Cell Biobank is the world's largest collection of tick cell lines, with a remit to store and distribute these cell lines to researchers in the UK and worldwide, to genotypically and phenotypically characterise selected existing cell lines and to generate new cell lines from tick species and strains not already represented in the collection with an emphasis on those of importance in lower- and middle-income countries (LMIC). In addition we aim to generate cell lines from other neglected arthropods of LMIC importance including midges, sand flies and mites. Since the start of this grant, two new tick cell lines and one sand fly cell line have been established and several other tick, sandfly and midge cell lines are under development (a process which takes between 1 and 7 years). Provision of tick cell lines to collaborators all over the world has led to scientific advancement in a wide range of research areas; for example, in vitro systems are now available for propagation of the human pathogens Crimean-Congo haemorrhagic fever virus, Candidatus Neoehrlichia mikurensis and Mycobacterium leprae in tick cells, the role of tick innate immunity in transmission of pathogens such as tick-borne encephalitis virus is now being determined, and tick cell lines are helping to elucidate how ticks develop resistance to acaricides (chemicals used to control ticks).
Exploitation Route External and internal use of tick cell lines from the Tick Cell Biobank, and associated collaborative research, is a continuous, ongoing process, as evidenced by the 47 first-, senior- or co-authored papers listed in the Common Outcomes of the previous BBSRC-funded Tick Cell Biobank project (BBS/E/I/00001741). Six of those are also attributed to this grant along with four more recent papers . Further collaborative manuscripts are in press (x 1), under review (x 2) or nearly ready for submission (x 2). Papers co-authored by Tick Cell Biobank staff or students comprise less than 30% of all papers reporting use of tick cell lines and published since 2010, a clear indication of how other scientists worldwide are exploiting these tools in their research. As and when new cell lines become established from additional species of ticks and other neglected arthropods, these will be added to the collection and made available as research tools for UK and international scientists working on pathogens transmitted by these arthropod species. In particular, uptake by LMIC scientists will be facilitated by our sister project (BB/P024378/1) in which outposts of the Tick Cell Biobank are being set up in Malaysia, Kenya and Brazil. A new and growing area of interest is use of tick cell lines in development of novel and improved tick control methods (screening of potential acaricidal compounds and plant products, anti-tick vaccine development). Another research area of huge potential impact is the development of an in vitro culture system in tick cell lines for Mycobacterium leprae, the causative agent of human leprosy which was previously uncultivable.
Sectors Agriculture, Food and Drink,Chemicals,Education,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology,Other

URL https://www.liverpool.ac.uk/infection-and-global-health/research/tick-cell-biobank/
 
Description BBSRC-NRF Newton-Utafiti fund call in enhancing ruminant livestock productivity
Amount £150,797 (GBP)
Funding ID BB/S004890/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2019 
End 01/2020
 
Description Defra Veterinary Medicines Directorate (VMD) Tender Reference: ITT_4649 (project_23900), Lot 3: Bees
Amount £399,924 (GBP)
Organisation Department For Environment, Food And Rural Affairs (DEFRA) 
Sector Public
Country United Kingdom
Start 04/2019 
End 03/2023
 
Description H2020-SFS-2016-2017 (Sustainable Food Security - Resilient and resource-efficient value) as part of consortium PALE-Blu including ILRI, Pirbright and Tick Cell Biobank
Amount € 6,039,301 (EUR)
Funding ID 727393 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 09/2017 
End 11/2020
 
Description Newton Fund Institutional Links
Amount £149,930 (GBP)
Funding ID 332192305 
Organisation British Council 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2018 
End 03/2020
 
Title Sand fly cell line LLE/LULS40 
Description Cell line derived from embryos of the Brazilian sand fly Lutzomyia longipalpis; currently at passage 14 after 3 years in vitro. 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact This is the third L. longipalpis cell line known to exist; the others were established in USA and Brazil, and are not held in any international culture collections. LLE/LULS40 will be made available to researchers worldwide through the Tick Cell Biobank and will therefore have potential for widespread use in research on sand flies and the viral and protozoan pathogens they transmit. It is also the first insect cell line to be established by the Tick Cell Biobank, providing proof of concept that techniques applied to ticks can be successfully adapted for application to insects and other arthropods. 
 
Title Tick cell line ARE/LULS41 
Description Cell line derived from embryos of the argasid (soft) tick Argas reflexus, which infests pigeons; currently at passage 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact This is the first cell line derived from this tick genus, and brings the number of soft tick cell lines to 12 (the remainder are derived from Ornithodoros moubata and Carios capensis). Unlike the Carios and Ornithodoros cell lines that are difficult or impossible to cryopreserve, ARE/LULS41 was successfully cryopreserved and resuscitated at passage 3 following standard techniques for tick cell lines; this demonstrates that inability to freeze is not a characteristic of soft tick cells per se. 
 
Title Tick cell line HDE/LURF39 
Description Cell line derived from embryos of the tick Hyalomma dromedarii; currently at passage 6 after 8 years in vitro 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact This cell line is the third continuous cell line derived from embryonic Hyalomma dromedarii, the camel tick, from East Africa. All three cell lines have potential application in study of bacterial and viral camel pathogens, as well as wider application in study of human pathogens transmitted by Hyalomma spp. ticks, in particular Crimean-Congo hemorrhagic fever virus. 
 
Title Tick cell line HLE/LULS42 
Description Cell line derived from embryos of the tick Hyalomma lusitanicum from Spain, currently at passage 4 after 5 years in vitro 
Type Of Material Cell line 
Year Produced 2019 
Provided To Others? No  
Impact This is the first cell line to be develoiped from Hyalomma lusitanicum, an important tick in Spain and the first tick species to be found to harbour the human pathogen Crimean-Congo hemorrhagic fever virus in Spain. 
 
Description Armed Forces Research Institute of Medical Sciences, Thailand 
Organisation Armed Forces Research Institute of Medical Sciences
Country Thailand 
Sector Public 
PI Contribution We have sequenced the genome of the main scrub typhus vector, Leptotrombidium deliense, a chigger mite. We will attempt to establish a chigger cell line using material supplied by AFRIMS.
Collaborator Contribution AFRIMS will supply fresh chigger mite material for attempts in cell line establishment.
Impact No outputs to date. Not multi-disciplinary.
Start Year 2018
 
Description Collaboration with ANSES Paris on tick-borne virus propagation in tick cell lines 
Organisation French Agency for Food, Environmental and Occupational Health & Safety (ANSES)
Country France 
Sector Public 
PI Contribution I have provided them with tick cell lines and associated training for use in the ARBONET project in which we are both partners
Collaborator Contribution They will share results with me from their experiments on propagation of West Nile virus in tick cell lines.
Impact No outcomes yet
Start Year 2016
 
Description Collaboration with Beijing Institute of Microbiology and Epidemiology on tick-borne bacteria 
Organisation Beijing Institute of Microbiology and Epidemiology
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance
Collaborator Contribution The partners funded me to visit their laboratory for a week to provide tick cell training, present a seminar and discuss future collaborations.
Impact None so far
Start Year 2016
 
Description Collaboration with CIBIR, La Rioja, Spain on generation of cell lines from Spanish ticks and tick-borne bacteria 
Organisation Spanish National Research Council (CSIC)
Department Biological Research Center
Country Spain 
Sector Private 
PI Contribution This collaboration started prior to the start of the present project. I provided the partners with a panel of tick cell lines and training in their maintenance. I also provided training in tick cell line establishment. I have hosted a PhD student for three collaborative visits to The Pirbright Institute, in 2014, 2015 and 2017. I hosted the same scientist, now post-doctoral, for a collaborative visit to the University of Liverpool in 2019.
Collaborator Contribution The partners used the tick cell lines in experiments which led to several joint conference posters and three joint publications, with another manuscript in preparation. The partners provided me with engorged female ticks of several species from Spain, enabling me to prepare primary cell cultures with a view to cell line establishment. The visiting PhD student assisted me in screening tick cell lines for endosymbiotic or contaminating bacteria. The visiting post-doctoral scientist assisted me in identifying tick-borne bacteria isolated in tick cell lines.
Impact Joint publications: http://dx.doi.org/10.1016/j.micinf.2015.09.018 http://dx.doi.org/10.1016/j.vetmic.2015.07.008 http://dx.doi.org/10.1016/j.ttbdis.2015.05.002 https://doi.org/10.1016/j.ttbdis.2019.02.008 Joint funding proposals to EU H2020 MSCA ITN programme in 2015 and 2016 (unsuccessful)
Start Year 2011
 
Description Collaboration with CVR on tick-borne viruses 
Organisation University of Glasgow
Department School of Engineering Glasgow
Country United Kingdom 
Sector Academic/University 
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance
Collaborator Contribution The partners used the tick cell lines in experiments that led to a joint publication
Impact Joint publication: https://doi.org/10.1093/nar/gku657
Start Year 2011
 
Description Collaboration with Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russia, on TBEV and generation of tick cell lines 
Organisation Russian Academy of Medical Sciences
Department Chumakov Institute of Poliomyelitis and Viral Encephalitides
Country Russian Federation 
Sector Academic/University 
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance, and set up primary cell cultures with a view to cell line establishment from two species of Russian ticks. This work started before I joined the Pirbright Institute, but has continued ever since
Collaborator Contribution The partners provided me with engorged female Dermacentor reticulatus and D. marginatus ticks from their laboratory colony for cell line establishment. They used the tick cell lines that I provided in experiments that have led to a joint manuscript submitted for publication, poster presentations and a PhD thesis.
Impact Joint manuscript submitted: Belova, O.A., Litov, A.G., Kholodilov, I.S., Kozlovskaya, L.I., Bell-Sakyi, L., Romanova, L.I., Karganova, G.G. (submitted). Properties of tick-borne encephalitis virus populations during persistent infection of ixodid ticks and tick cell lines. Ticks and Tick-borne Diseases. One putative cell line from Dermacentor reticulatus and two putative cell lines from D. marginatus ticks
Start Year 2011
 
Description Collaboration with FLI Riems on soft ticks and tick-borne viruses 
Organisation Friedrich Loeffler Institute
Country Germany 
Sector Public 
PI Contribution I provided the partners with a panel of cell lines derived from the soft tick Ornithodoros moubata and training in their maintenance. I am attempting to establish cell lines from the soft ticks Argas reflexus and Ornithodoros erraticus provided by the partners.
Collaborator Contribution The partners are carrying out transcriptomic analysis of the O. moubata cell lines and attempting to infect them with African swine fever virus. They provided me with engorged female A. reflexus and O. erraticus ticks for primary cell cultures with a view to cell line establishment.
Impact Argas reflexus embryo-derived cell line ARE/LULS41
Start Year 2015
 
Description Collaboration with Fiocruz on Tick Cell Biobank 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Country Brazil 
Sector Public 
PI Contribution Collaboration on establishment of Tick Cell Biobank Outpost at Fiocruz
Collaborator Contribution Agreement to house an Outpost of the Tick Cell Biobank and willingness to integrate the Biobank Outpost into the Fiocruz Collections, which will secure its future after the end of BBSRC funding.
Impact The Brazilian Tick Cell Biobank Outpost is currently in the process of establishment.
Start Year 2017
 
Description Collaboration with ILRI Tick Unit 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution The ILRI Tick Unit is a partner in the project "GCRF-BBR: The Tick Cell Biobank: outposts in Asia, Africa and South America, and will host the African Outpost. We will provide training in managing the Outpost and maintaining and generating tick cell lines, and stock the Outpost with a panel of the most popular and regionally relevant tick cell lines for local and regional distribution and use.
Collaborator Contribution The ILRI Tick Unit will house and manage the African Outpost of the Tick Cell Biobank. In addition they will provide us with, as and when available, samples of local tick species for novel cell line establishment and genetic analysis.
Impact No outputs yet
Start Year 2015
 
Description Collaboration with IREC (Instituto de Investigacion en Recursos Cinegeticos), Spain 
Organisation Institute for Game and Wildlife Research
Country Spain 
Sector Academic/University 
PI Contribution I provided my collaborators (Prof. Jose de la Fuente and members of his research group) with a panel of tick cell lines from the Tick Cell Biobank over several years (commencing when the Tick Cell Biobank was located at The Roslin Institute, University of Edinburgh prior to its move to The Pirbright Institute), training in their maintenance and ongoing advice and support. I helped to write manuscripts describing the results of their research with the tick cell lines, which have been published in international peer-reviewed scientific journals.
Collaborator Contribution My collaborators carried out research into a variety of topics relating to ticks and tick-borne pathogens using the tick cell lines that I provided, and published the results in a series of co-authored manuscripts, conference posters and PhD theses.
Impact 7 papers published in peer-reviewed international scientific journals since the start of the present project: DOI: 10.1186/1756-3305-7-42 http://dx.doi.org/10.1371/journal.pone.0137237 DOI: 10.1186/s13071-015-1210-x http://dx.doi.org/10.1371/journal.pone.0133038 DOI 10.1074/mcp. M115.051938 http://dx.doi.org/10.1016/j.ttbdis.2015.07.001 Mansfield, K.L., Cook C., Ellis, R., Bell-Sakyi, L., Johnson, N., Alberdi, P., de la Fuente, J., Fooks, A.R. (in press). Tick-borne pathogens induce differential expression of genes promoting cell survival and host resistance in Ixodes ricinus cells. Parasites & Vectors
Start Year 2009
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation Government of Sweden
Department Swedish Institute for Infectious Disease Control
Country Sweden 
Sector Public 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation Karolinska Institute
Country Sweden 
Sector Academic/University 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with Karolinska, SVA and Swedish Public Health Agency on CCHFV 
Organisation National Veterinary Institute
Country Sweden 
Sector Public 
PI Contribution I provided the collaborators with tick cell lines for propagation of Crimean-Congo hemorrhagic fever virus, and ongoing technical advice on their maintenance
Collaborator Contribution The collaborators used the tick cell lines to propagate CCHFV under BSL4 conditions, and a non-pathogenic relative Hazara virus under BSL2 conditions.
Impact A jointly co-authored poster "Nairoviruses chronically infected Hyalomma-derived cell lines" (Salato, C., Karlberg, H., Bell-Sakyi, L., Palu, G., Mirazimi, A.) was presented at the 5th European Virology Congress in Lyon in 2013. A joint funding proposal was submitted to the third ANIHWA call; this was awarded and started in 2016. The project is coordinated by Prof Ali Mirazimi, Karolinska Institute, and Dr Lesley Bell-Sakyi is the Pirbright PI.
Start Year 2012
 
Description Collaboration with SAS Institute of Zoology and University of Salford on tick-borne microorganisms 
Organisation Slovak Academy of Sciences
Department Institute of Zoology
Country Slovakia 
Sector Academic/University 
PI Contribution I isolated tick-borne microorganisms from Slovakian ticks provided by SAS and propagated them in tick cell lines, leading to a joint publication
Collaborator Contribution SAS provided ticks from which microorganisms were isolated, leading to a joint publication. University of Salford characterized a trypanosome isolated from a Slovakian tick, leading to a joint manuscript in preparation.
Impact Joint publication: http://dx.doi.org/10.1016/j.ttbdis.2015.05.002
Start Year 2014
 
Description Collaboration with SAS Institute of Zoology and University of Salford on tick-borne microorganisms 
Organisation University of Salford
Department Sustainable Housing & Urban Studies Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution I isolated tick-borne microorganisms from Slovakian ticks provided by SAS and propagated them in tick cell lines, leading to a joint publication
Collaborator Contribution SAS provided ticks from which microorganisms were isolated, leading to a joint publication. University of Salford characterized a trypanosome isolated from a Slovakian tick, leading to a joint manuscript in preparation.
Impact Joint publication: http://dx.doi.org/10.1016/j.ttbdis.2015.05.002
Start Year 2014
 
Description Collaboration with TIDREC, University of Malaya 
Organisation University of Malaya
Country Malaysia 
Sector Academic/University 
PI Contribution I provided TIDREC with a panel of tick cell lines for use in isolation and cultivation of viruses and training in both maintenance of tick cell lines and establishment of primary tick cell cultures with a view to establishment of cell lines from Malaysian ticks.
Collaborator Contribution TIDREC paid for me to visit their laboratories in August 2014 to participate in a tick workshop, deliver on-site training in tick cell line maintenance and primary cell culture establishment, and to discuss and plan future collaborative projects.
Impact Two joint publications: http://doi.org/10.11158/saa.22.3.1 and doi:10.1038/srep14007 Three joint grant proposals: Two proposals to EU H2020 MSCA ITN in 2015 and 2016 (Coordinator Lesley Bell-Sakyi, TIDREC was one of 9 partners), both unsuccessful though second proposal was highly rated; one BBSRC BBRF-GCRF proposal under consideration (PI Ben Makepeace, University of Liverpool, TIDREC is one of 3 LMIC partners).
Start Year 2011
 
Description Collaboration with The Pirbright Institute 
Organisation The Pirbright Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing RNA etxracted from arbovirus-infected tick cell lines for transcriptomic analysis as part of the ARBONET project I am generating a novel cell line from the UK midge Culicoides nubeculosus which will be shared with Pirbright as part of the EU-funded PALE-Blu project
Collaborator Contribution Pirbright are carrying out collaborative RNA sequencing and transcriptomic analysis of arbovirus-infected tick and mosquito cells as part of the ARBONET project. The Pirbright Insectary provided the Tick Cell Biobank with eggs from C. nubeculosus midges for cell line establishment.
Impact None so far
Start Year 2017
 
Description Collaboration with UFRRJ 
Organisation Federal Rural University of Rio de Janeiro
Country Brazil 
Sector Academic/University 
PI Contribution The Tick Cell Biobank has had an ongoing collaboration with UFRRJ since 2009, when a senior UFRRJ staff member spent a four-month training sabbatical in the Tick Cell Biobank (then at the University of Edinburgh). We then provided them with a panel of tick cell lines that they have used in collaborative research. They will provide expertise and some tick cell lines to the South American Outpost of the Tick Cell Biobank that will be established at a neighbouring institute (Oswaldo Cruz Institute in Rio de Janeiro) with which we have a three-way collaboration.
Collaborator Contribution UFRRJ deposited in the Tick Cell Biobank a primary tick cell culture that they set up from locally-sourced Rhipicephalus microplus ticks; this culture subsequently developed into the cell line BME/PIBB36, which will be the first tick cell line of Brazilian origin to be available for international distribution.
Impact Tick cell line BME/PIBB36, derived from embryonic Rhipicephalus microplus ticks from Seropedica, Brazil. Four collaborative research papers: http://dx.doi.org/10.1590/1414-431X20165211;  https://doi.org/10.1017/pao.2017.17; https://doi.org/10.1017/pao.2018.6; https://doi.org/10.1371/journal.pntd.0007001
Start Year 2009
 
Description Collaboration with UFRRJ and Fiocruz on tick-borne bacteria and generation of cell lines from Brazilian ticks 
Organisation Federal Rural University of Rio de Janeiro
Country Brazil 
Sector Academic/University 
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance, and training in establishment of embryo-derived tick cell lines
Collaborator Contribution The partners have used the tick cell lines in experiments leading to a joint publication on Borrelia burgdorferi in tick cells and a manuscript in preparation on growth of Mycobacterium leprae in tick cell lines. UFRRJ deposited a primary cell culture derived from Brazilian Rhipicephalus microplus in the Tick Cell Biobank which has now yielded a continuous cell line.
Impact Joint publication: http://dx.doi.org/10.1590/1414-431X20165211 New tick cell line BME/PIBB36 Joint funding applications - Newton Fund, MRC, Newton Advanced Fellowship (all unsuccessful); BBSRC BBRF-GCRF (under consideration)
Start Year 2009
 
Description Collaboration with UFRRJ and Fiocruz on tick-borne bacteria and generation of cell lines from Brazilian ticks 
Organisation Oswaldo Cruz Foundation (Fiocruz)
Country Brazil 
Sector Public 
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance, and training in establishment of embryo-derived tick cell lines
Collaborator Contribution The partners have used the tick cell lines in experiments leading to a joint publication on Borrelia burgdorferi in tick cells and a manuscript in preparation on growth of Mycobacterium leprae in tick cell lines. UFRRJ deposited a primary cell culture derived from Brazilian Rhipicephalus microplus in the Tick Cell Biobank which has now yielded a continuous cell line.
Impact Joint publication: http://dx.doi.org/10.1590/1414-431X20165211 New tick cell line BME/PIBB36 Joint funding applications - Newton Fund, MRC, Newton Advanced Fellowship (all unsuccessful); BBSRC BBRF-GCRF (under consideration)
Start Year 2009
 
Description Collaboration with URMITE on tick-borne bacteria and establishment of cell lines from French ticks 
Organisation Aix-Marseille University
Country France 
Sector Academic/University 
PI Contribution I provided the partners with a panel of tick cell lines and training in their maintenance. I have established a cell line from embryonic Rhipicephalus sanguineus ticks provided by the partners.
Collaborator Contribution The partners have used the tick cell lines for a variety of studies on tick-borne bacteria, leading to two joint publications.
Impact Joint publications: http://dx.doi.org/10.1016/j.ttbdis.2012.10.016 DOI: 10.1186/1944-3277-9-9 Tick cell line RSE/PILS35
Start Year 2009
 
Description Collaboration with University Hospital Heidelberg on tick-borne phleboviruses 
Organisation Heidelberg University Hospital
Country Germany 
Sector Hospitals 
PI Contribution I provided tick cell lines and training in their maintenance
Collaborator Contribution The partners carried out experiments using the tick cell lines that I provided and generated data for a collaborative paper
Impact Joint publication: doi:10.1128/JVI.00095-16
Start Year 2014
 
Description Collaboration with University of Gothenburg 
Organisation University of Gothenburg
Department Institute of Biomedicine
Country Sweden 
Sector Academic/University 
PI Contribution The Tick Cell Biobank provided two tick cell lines and trained a laboratory technician in tick cell line maintenance. We provided follow-up support to assist the Swedish team in establishing tick cells in their laboratory, and subsequently isolating for the first time the emerging human pathogen Candidatus Neoehrlichia mikurensis in the tick cells. Lesley Bell-Sakyi helped to draft and revise a manuscript reporting the results.
Collaborator Contribution The partners wrote a paper, upon which Lesley Bell-Sakyi is a co-author, reporting the first successful isolation and propagation of Neoehrlichia mikurensis in tick, and subsequently human, cells. This paper was accepted by Emerging Microbes and Infection and is "in press". The N. mikurensis isolates will be deposited in the Tick Cell Biobank for in-house use and onward distribution to the scientific community.
Impact First successful isolation and cultivation of multiple isolates of the emerging human tick-borne bacterial pathogen Neoehrlichia mikurensis Paper in press: Wass, L., Grankvist, A., Bell-Sakyi, L., Bergström, M., Ulfhammer, E., Lingblom, C., Wennerås, C. (2019). Cultivation of the causative agent of human neoehrlichiosis from clinical isolates identifies vascular endothelium as a target of infection. Emerging Microbes and Infections.
Start Year 2015
 
Description Collaboration with University of Lancaster on sand fly cell lines 
Organisation Lancaster University
Country United Kingdom 
Sector Academic/University 
PI Contribution I am generating cell lines from multiple strains of the Brazilian sand fly species Lutzomyia longipalpis that express different pheromone types.
Collaborator Contribution My colleague at University of Lancaster is providing the starting material (sand fly eggs) for generation of primary cell cultures and subsequently cell line(s)
Impact Sand fly cell line LLE/LULS40
Start Year 2015
 
Description Collaboration with University of Nottingham 
Organisation University of Nottingham
Department School of Veterinary Medicine and Science Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution I am generating novel cell lines from UK, European, African and Middle Eastern midge species as part of the EU-funded PALE-Blu consortium. This work is done under sub-contract to University of Nottingham.
Collaborator Contribution As part of the ARBONET project, a University of Nottingham staff member has provided training to my team in virus culture and monitoring, and is involved in transcriptomic analysis of arbovirus-mosquito interactions.
Impact None yet
Start Year 2017
 
Description Collaboration with University of Parma and SVA on acaricide resistance 
Organisation National Veterinary Institute
Country Sweden 
Sector Public 
PI Contribution I provided tick cell lines and training in their maintenance
Collaborator Contribution The partners used the tick cell lines in experiments which resulted in a joint publication and a second manuscript in preparation
Impact Joint publication: DOI: 10.1186/s13071-016-1497-2
Start Year 2013
 
Description Collaboration with University of Parma and SVA on acaricide resistance 
Organisation University of Parma
Department Department of Veterinary Science
Country Italy 
Sector Academic/University 
PI Contribution I provided tick cell lines and training in their maintenance
Collaborator Contribution The partners used the tick cell lines in experiments which resulted in a joint publication and a second manuscript in preparation
Impact Joint publication: DOI: 10.1186/s13071-016-1497-2
Start Year 2013
 
Description Collaboration with the Moredun Research Institute (Mite cell lines) 
Organisation Moredun Research Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution I provide training to a member of MRI staff in arthropod cell culture generation, generate primary cell cultures and maintain them at Pirbright with a view to cell line establishment.
Collaborator Contribution MRI provide the poultry mites that are starting material for the generation of primary cell cultures and work with me to establish protocols for surface-sterilization and initial cell culture generation.
Impact So far we have established a protocol for successful harvesting and surface-sterilisation of poultry mite eggs, which is an essential first step to obtaining primary cell cultures.
Start Year 2015
 
Description UK Environment Agency 
Organisation Environment Agency
Country United Kingdom 
Sector Public 
PI Contribution We are attempting to establish a cell line from freshwater fish lice (Argulus spp.) and have sequenced the genome of A. japonicus, which may lead to the development of novel control options.
Collaborator Contribution The Environment Agency has supplied viable and fixed Argulus specimens for cell line development and genome sequencing.
Impact No outputs to date. Not multidisciplinary.
Start Year 2017
 
Description Meet the Scientists 
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 Organised by the University of Liverpool's Faculty of Health and Life Sciences and supported by the Wellcome Trust, the programme aims to share the global impact of Liverpool research through fun and engaging activities and demonstrations. Staff and students from the Institute of Infection and Global Health hosted the first event on 24th November 2018 at Liverpool's World Museum. The theme was "Bacteria. Viruses. Parasites. They're everywhere. Come along and learn about all things infectious, how these organisms spread, and how we can prevent them spreading". Project staff manned stalls on parasites (including ticks) and biomarkers of infection, and interacted with members of the public of all ages from toddlers to grandparents.
Year(s) Of Engagement Activity 2018
URL https://news.liverpool.ac.uk/2018/11/23/new-series-of-meet-the-scientists-begins-this-weekend/