GCRF-BBR: The Tick Cell Biobank: outposts in Asia, Africa and South America

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. These diseases are caused by viruses, bacteria, protozoa and filarial worms. While ticks and tick-borne diseases (TBD) occur worldwide, the economic burden they impose falls disproportionately on least-developed and lower-middle-income countries (LMIC) in the tropics and sub-tropics. Losses are incurred through direct costs of tick and TBD control (acaricides, antibiotic and antiparasitic treatment, vaccines where these exist) and indirect costs of reduced productivity, mortality and time and manpower expended on applying control measures. Development of resistance by ticks to existing acaricides is an increasing problem worldwide, and major pharmaceutical companies are unwilling to invest in new chemical tick control approaches for the livestock sector in LMIC. To reduce the economic burden on smallholder farmers and livestock owners in LMIC, new acaricides and/or alternative tick control regimes, and affordable and effective vaccines and/or drug treatments for TBD, are urgently needed.

Research into prevention and cure of these diseases 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. Tick cell lines are increasingly important research tools for study of tick-associated problems affecting LMIC; since they are relatively cheap and easy to grow, they enable many laboratories that lack infrastructure for feeding ticks on large animals to carry out many aspects of tick and TBD research. Seven years ago a central repository, the Tick Cell Biobank, was created in the UK for all the tick cell lines available now and in future. The Tick Cell Biobank distributes tick cell lines on request to research scientists and provides essential training in their maintenance. Currently it is difficult and expensive for LMIC researchers to obtain and maintain existing tick cell lines to support their tick and TBD research, as the cells must be imported from the UK and local training is unavailable. To address this issue and improve LMIC access to tick cell lines and associated expertise, we will establish regional outposts of the Tick Cell Biobank in Malaysia, Kenya and Brazil. The outposts will be sited at institutes with existing tick and/or TBD-related research programmes, in collaboration with experiences local scientists, and will offer a regionally-tailored portfolio of tick cell lines with training in their maintenance. We will also encourage establishment of novel cell lines from indigenous tick species by sharing expertise in the required techniques. We anticipate that the Tick Cell Biobank outposts will enable scientists in these and neighbouring countries to fully exploit the potential of TCL in their research. In the long term, this will build and expand local capacity for tick and TBD research, leading to more and better locally generated solutions for local and regional problems.

Technical Summary

Ticks and tick-borne diseases are a huge economic drain on the resources of LMIC in the tropics and sub-tropics. There is a growing unmet need for development of novel control methods for ticks to replace existing acaricides due to the rapid spread of resistance, and for effective, affordable and widely available vaccines for tick-borne diseases. Tick cell lines are playing an increasingly important and valuable role in research into many aspects of tick and tick-borne pathogen biology and control. The Tick Cell Biobank is a UK-based biological resource that underpins UK and international tick and tick-borne disease research. The Tick Cell Biobank houses and supplies over 50 cell lines derived from 15 ixodid and two argasid tick species of veterinary and/or medical importance, and provides recipient scientists with training in tick cell maintenance and cell line establishment. However LMIC scientists face difficulties in accessing tick cell lines; as a result they are underrepresented amongst recipients and unable to fully exploit this valuable resource in their research. This GCRF proposal, which forms a component of the BBRF proposal "The Tick Cell Biobank - a UK and international biological resource", aims to address the problem of LMIC access to tick cell lines by establishing outposts of the Tick Cell Biobank in South-East Asia (Malaysia), Africa (Kenya) and South America (Brazil). These outposts will stock and supply a targeted selection of the most popular and regionally-relevant tick cell lines, and provide training in their maintenance, to scientists within each region, thereby raising the profile of, and improving access to, these unique and valuable research tools. In the long term, this will build and expand local capacity for tick and tick-borne disease research in both veterinary and medical fields, leading to more and better locally generated solutions for local and regional problems.

Planned Impact

In addition to the academic beneficiaries listed in the previous section, the following groups should benefit from the proposed establishment of Tick Cell Biobank outposts in Malaysia, Kenya and Brazil in the short term:

- Scientific, legal and administrative staff of the three institutes housing the Tick Cell Biobank outposts will gain experience in managing an international culture collection, thereby enhancing their career development and employment prospects
- Links between the LMIC institutes involved in the project 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 in LMIC, in both veterinary and human medicine, will be raised

In the longer term, use of tick cell lines by LMIC researchers will facilitate i) delivery of 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:

- LMIC farmers and smallholders 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
- LMIC veterinarians will have access to improved products for diagnosis, treatment and control of ticks and tick-borne diseases affecting livestock and companion animals
- LMIC clinicians 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

The expertise in establishment of arthropod cell lines disseminated by the Tick Cell Biobank outposts will additionally benefit equivalent groups affected by arthropod vectors other than ticks (e.g. mites, sand flies, midges, lice, fleas) and the pathogens that these arthropods transmit, in ways similar to those outlined above.
 
Description All four specific objectives of the project are already partially met and we are on target to have three fully-established and functioning Tick Cell Biobank Outposts in Malaysia, Kenya and Brazil by the end of the project in 2020.
Exploitation Route Not applicable - project still in progress,
Sectors Agriculture, Food and Drink,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://www.liverpool.ac.uk/infection-and-global-health/research/tick-cell-biobank/outposts_project
 
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 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 Tick cell line BME/PIBB36 
Description Cell line derived from embryonic Rhipicephalus microplus ticks, currently at passage 10 after four years in vitro. Ready for dissemination through the Tick Cell Biobank 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact This cell line is the first derived from Brazilian ticks to be made available through the Tick Cell Biobank and the South American Outpost at Fiocruz in Rio de Janeiro. 
 
Title Tick cell line RAE/PIPM38 
Description Cell line derived from embryonic Rhipicephalus appendiculatus ticks, currently at passage 5 after 6 years in vitro. 
Type Of Material Cell line 
Year Produced 2018 
Provided To Others? Yes  
Impact None so far 
 
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 ILRI Tick Unit 
Organisation International Livestock Research Institute (ILRI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution We have submitted several successful grant proposals together - a BBSRC Other Countries Partnering Award (2015-2017), the BBSRC-GCRF-BBR project "The Tick Cell Biobank: outposts in Asia, Africa and South America" (2017-2020) and the BBSRC-funded Newton-Utafiti research project "The role of heartwater (Ehrlichia ruminantium infection) and other tick-borne pathogens in Acute Camel Death Syndrome in Kenya" (2019-2020, ACDS). We have trained two ILRI staff members and one ILRI-based MSc student in tick cell culture techniques.
Collaborator Contribution The ILRI Tick Unit is hosting one of the three Tick Cell Biobank Outposts, including running a training workshop for young African scientists in January 2020, and providing lab facilities and support for part of the lab work being carried out under the ACDS project. They are also hosting the University of Liverpool PDRA employed on the ACDS project for 4 months (Jan-April 2020).
Impact Successful funding proposals as outlined above.
Start Year 2015
 
Description Collaboration with Liverpool School of Tropical Medicine on insect cell line establishment 
Organisation Liverpool School of Tropical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution I am generating cell lines from insect (tsetse fly and sand fly) material provided by colleagues at LSTM
Collaborator Contribution My colleagues at LSTM provided me with insect eggs (sand fly) and larvae (tsetse fly) with which to generate primary cell cultures with a view to cell line establishment
Impact No outputs yet apart from primary cell cultures that may or may not develop into cell lines
Start Year 2018
 
Description Collaboration with London School of Hygiene and Tropical Medicine on insect cell line establishment 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution I am attempting to generate insect (triatomid bug) cell lines from starting material provided by my colleagues at LSHTM
Collaborator Contribution Colleagues at LSHTM are providing eggs of Triatoma infestans for generation of primary cell cultures with a view to cell line establishment
Impact no outputs yet
Start Year 2019
 
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 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 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 Swansea 
Organisation Swansea University
Country United Kingdom 
Sector Academic/University 
PI Contribution I am attempting to generate cell lines from the triatomid bug Rhodnius prolixus, vector of Chagas Disease, using material provided by a colleague at Swansea University
Collaborator Contribution My colleague at Swansea University has provided Rhodnius prolixus eggs for generation of primary cell cultures with a view to cell line establishment
Impact No outputs yet apart from primary R. prolixus cell cultures
Start Year 2019
 
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 2018,2019
URL https://news.liverpool.ac.uk/2018/11/23/new-series-of-meet-the-scientists-begins-this-weekend/