A Global Network for Neglected Tropical Diseases

Lead Research Organisation: Durham University
Department Name: Chemistry

Abstract

It is estimated that ~1 in 6 of the world's population suffer from a Neglected Tropical Disease (NTD) representing a significant challenge to global human health and well-being and this has been recognised by the United Nations (UN). One of the primary aims of the UN's Sustainable Development Goal on "Health and Well-Being" is to "ensure health and well-being for all" and with 1.7 billion people in 185 countries requiring treatment for at least one NTD in 2014, advances in the development of new medicines for NTDs is critical. Indeed, the target set by the UN is "By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases." Supporting the delivery of this goal are many world-wide ventures directed towards the treatment of AIDs (e.g. The Global Fund), tuberculosis (e.g. The Global Fund) and malaria (e.g. Medicines for Malaria Venture) but there is currently no corresponding world-wide sustained effort for NTDs. It is this gap that our global NTD network will fill and, in doing so, will contribute to the delivery of the UN's goal on "Health and Well-Being".

Within the spectrum of NTD pathogens, insect-borne parasites represent a major threat to human health across the developing world. In particular, leishmaniasis and Chagas disease represent a significant challenge for developing nations with lower levels of research investment and infrastructure exacerbated by a lack of suitably trained personnel capable of developing much needed solutions. With over 350 million people world-wide considered at risk, more than 1.7M new cases each year, 12 million people currently infected and an economic cost that can be estimated in terms of 2.4 million Disability Adjusted Life Years (DALYs), the health challenge of leishmaniasis is undeniable. A similar situation exists for Chagas disease where there are currently 10M people infected and, in Latin America alone, Chagas disease leads to approx.700,000 (DALYs), nearly six times the socioeconomic toll of malaria in the region. Globally, the total annual economic effect of Chagas disease is estimated at over $7 billion. The challenge presented by these disease states is heightened by the fact that the few efficacious drugs currently available often exhibit serious, potentially fatal, side-effects, and have difficult and prolonged modes of administration leading to poor patient compliance within developing nations. Moreover, reports of resistance to even the most modern drugs are beginning to emerge.

We will establish a "Global Network For Neglected Tropical Diseases" which will bring together over 50 academics and more that 500 researchers at 14 institutes around the world all working towards the common goals of delivering scientific advances that will help to combat Leishmaniasis and Chagas disease

Technical Summary

It is estimated that ~1 in 6 of the world's population suffer from a Neglected Tropical Disease (NTD) representing a significant challenge to global human health and well-being and this has been recognised by the United Nations (UN). One of the primary aims of the UN's Sustainable Development Goal on "Health and Well-Being" is to "ensure health and well-being for all" and with 1.7 billion people in 185 countries requiring treatment for at least one NTD in 2014, advances in the development of new medicines for NTDs is critical. Indeed, the target set by the UN is "By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases and combat hepatitis, water-borne diseases and other communicable diseases." Supporting the delivery of this goal are many world-wide ventures directed towards the treatment of AIDs (e.g. The Global Fund), tuberculosis (e.g. The Global Fund) and malaria (e.g. Medicines for Malaria Venture) but there is currently no corresponding world-wide sustained effort for NTDs. It is this gap that our global NTD network will fill and, in doing so, will contribute to the delivery of the UN's goal on "Health and Well-Being".

Within the spectrum of NTD pathogens, insect-borne parasites represent a major threat to human health across the developing world. In particular, leishmaniasis and Chagas disease represent a significant challenge for developing nations with lower levels of research investment and infrastructure exacerbated by a lack of suitably trained personnel capable of developing much needed solutions. With over 350 million people world-wide considered at risk, more than 1.7M new cases each year, 12 million people currently infected and an economic cost that can be estimated in terms of 2.4 million Disability Adjusted Life Years (DALYs), the health challenge of leishmaniasis is undeniable. A similar situation exists for Chagas disease where there are currently 10M people infected and, in Latin America alone, Chagas disease leads to approx.700,000 (DALYs), nearly six times the socioeconomic toll of malaria in the region. Globally, the total annual economic effect of Chagas disease is estimated at over $7 billion. The challenge presented by these disease states is heightened by the fact that the few efficacious drugs currently available often exhibit serious, potentially fatal, side-effects, and have difficult and prolonged modes of administration leading to poor patient compliance within developing nations. Moreover, reports of resistance to even the most modern drugs are beginning to emerge.

We will establish a "Global Network For Neglected Tropical Diseases" which will bring together over 50 academics and more that 500 researchers at 14 institutes around the world all working towards the common goals of delivering scientific advances that will help to combat Leishmaniasis and Chagas disease

Planned Impact

The significant social, developmental and economic impacts of Neglected Tropical Diseases (NTDs) on the World's poor are now recognised and efforts such as the World Health Organization 2020 Roadmap on NTDs and the London Declaration (2012) have raised the global profile within academic and industrial communities. The capacity to deliver new, effective therapies is often challenged by a lack of robust target validation tools and/or a lack of trained personnel with appropriate experience and expertise in both the UK and endemic ODA countries. We will address these twin capacity/capability deficiencies by establishing an active and sustainable global network of researchers, working collaboratively to develop and share new chemical and genetic technologies for drug target validation for the NTDs, leishmaniasis and Chagas disease. The network's 'open science' approach to knowledge transfer will facilitate the development of capacity and key capabilities in cell technology, chemical biology and assay development. These skills are vital to kick start interactions with both academic and industrial partners, providing robustly validated targets for downstream drug discovery initiatives. The network will deliver training, career development and collaborative opportunities to researchers at all career stages, from PhD-level to established academics. Training will be delivered via multiple pathways including research secondments and travel bursaries, training workshops in key skills and science 'sandpit' events. This will deliver >500 researchers ready to provide the skills and expertise, chemical and genetic, to address drug target validation challenges both in NTDs and other disease states. By providing new targets and assays our scientists and outputs will directly enhance academic communities interested in delivering new therapies to tackle diseases of poverty across the globe. In addition, the skills, focus and research outputs of our researchers will enable successful collaborations, grant applications and career independence. In addition to network and wider academic impact, potential impacts of the network's research on many non-academic stakeholder groups are described below:

Beneficiary 1: The pharmaceutical sector with a commitment to developing new therapies for the control of NTDs, particularly leishmaniasis and Chagas disease. Our research outcomes will benefit the pharma sector by [a] validating and characterizing novel drug targets in Leishmania spp and T. cruzi; [b] developing enzyme assay platforms for the screening of compound libraries; [c] developing a pool of dedicated, highly trained scientists focused on NTD target validation.

Beneficiary 2: The international knowledge economy through skills, training and development. All network participants will develop expertise in interdisciplinary research skills in chemical and/or genetic target validation and assay development. This skills profile is of great value to international industry in the knowledge economy, contributing to boosting the profile of NTDs in the pharmaceutical and other sectors.

Beneficiary 3: International development. Our international ODA partners are resident in endemic countries in which leishmaniasis and Chagas disease are a major cause of economic loss through their effects on human health and development.

Beneficiary 4: The wider, international general public. Public understanding of sciences is a vital function of active research and is especially important for the NTDs, both in the UK and in endemic nations. Utilizing existing structures and creating new social media initiatives the research network will ensure that the wider public are engaged via, for example: [a] a network webpage; [b] researcher blogs; [c] the construction of thematic Wikipedia pages; and [d] engagement with local outreach programmes

Also see Pathways to Impact for details on the mechanism that will be used to reach the beneficiaries.

Publications

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Description Federal University of Minas Gerais (UFMG) (Brazil) Department of Biochemistry and Immunology 
Organisation Federal University of Minas Gerais
Department Dept of Biochemistry and Immunology
Country Brazil 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: Department of Biochemistry and Immunology: Prof. S.M. Teixeira [IC](immunology, parasite gene regulation, molecular biology of T.cruzi), Department of Parasitology: Prof. D.C. Bartholomeu (Genomics, surface antigens of T.cruzi, diagnostics) and Prof. R.T. Fujiwara (immunology, Leishmania and T.cruzi diagnostics)
Impact None yet
Start Year 2017
 
Description Federal University of Rio Grande do Sul (UFRGS)(Brazil) Department of Organic Chemistry 
Organisation Federal University of Rio Grande do Sul
Country Brazil 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: ) Department of Organic Chemistry: Prof. A. Pohlmann [IC](organic chemistry, polymeric delivery systems, transdermal delivery), College of Pharmacy: Prof. S. Stanisçuaski Guterres (pharmacy, polymeric delivery systems).
Impact none yet
Start Year 2017
 
Description Federal University of Rio de Janeiro (UFRJ)(Brazil) Institute of Biophysics 
Organisation Federal University of Rio de Janeiro
Country Brazil 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: Prof. B. Rossi-Bergmann [IC] (Molecular parasitology, pharmaceutics); Prof. L. Mendes (pharmacy, nanocrystals); Prof. R. Coutinho (Immunology, purinergic receptors) and Dr A. P. Lima (Immunology, animal models, parasitology) Federal
Impact none yet
Start Year 2017
 
Description National University of Rosario (NUR) (Argentina) School of Pharmacy and Biochemistry 
Organisation National University of Rosario
Country Argentina 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: School of Pharmacy and Biochemistry: Prof. G. R. Labadie [IC](organic synthesis, medicinal chemistry, chemical-biology); Dr. E.O.J. Porta (chemical biology, molecular modelling), Dr. C. Delpiccolo (catalysis, medicinal chemistry), Dr. A. La Venia (solid phase synthesis, peptides and peptidomimetics), Prof. J. A. Cricco (parasitology, microscopy, biophysics)
Impact None yet
Start Year 2017
 
Description State University of Campinas (UNICAMP) (Brazil) Department of Animal Biology 
Organisation State University of Campinas
Country Brazil 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: Department of Animal Biology: Dr. A.C. Coelho [IC](drug resistance, molecular diagnosis, chemotherapy of leishmaniasis); and Dr. D.C. Miguel (drug screening, chemotherapy of leishmaniasis).
Impact None yet
Start Year 2017
 
Description University of Buenos Aires (UBA) (Argentina) Medical Research Institute 
Organisation University of Buenos Aires
Country Argentina 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: laboratory of Molecular Parasitology: Dr. C. A. Pereira [IC] (target validation in Trypanosoma cruzi, drug discovery, virtual screening, medicinal chemistry)
Impact None yet
Start Year 2017
 
Description University of Karachi (UoK)(Pakistan) - International Centre for Chemical and Biological Sciences 
Organisation University of Karachi
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: Prof. I. Choudhary [HUB Leader][IC](Medicinal chemist); Prof. K.M. Khan (Medicinal chemist), Dr. A. Wahab (Structural Biologist), Dr. S. Yousuf (Natural Product chemist), Dr. S. Ahmed (Microbiologist), and Dr. S. Farooq (Microbiologist).
Impact None yet
Start Year 2017
 
Description University of São Paulo (USP)(Brazil) Institute of Biomedical Sciences 
Organisation University of Sao Paulo
Department Institute of Biomedical Sciences
Country Brazil 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise in the following: Prof. A. Silber biochemistry, genetics, molecular biology of T. cruzi; Department of Parasitology: Dr. SR. Uliana [IC](chemotherapy of leishmaniasis, drug assay development); Dr. JMP. Alves (Genomics, Bioinformatics, Parasitology); Institute of Tropical Medicine of São Paulo: Dr. PC. Cotrim (molecular diagnosis, drug resistance) and Dr. JAL. Lindoso (chemotherapy of leishmaniasis, diagnosis of infectious diseases, HIVLeishmania co-infection). Ribeirão Preto campus. Prof. A.Cruz (Genetics, Parasitology) and Dr L.Tosi (Leishmania, DNA replication biology)
Impact None yet
Start Year 2017
 
Description University of York (UoY)(UK) Centre for Immunology and Infection 
Organisation University of York
Department Centre for Immunology and Infection
Country United Kingdom 
Sector Academic/University 
PI Contribution Durham University has taken the lead of the Global network for neglected tropical diseases, it contributes the following expertise: Department of Chemistry: Prof. G. Sandford, PI (organic synthesis, organofluorine chemistry); Prof. P. Steel (organic synthesis, chemical probes, chemical-biology); Dr S. Cobb [IC](peptide chemistry, medicinal-chemistry, chemical-biology); Dr R. Pal (diagnostics, cell based imaging, microscopy) and Dr R. Kataky (biomarkers, diagnostics, drug delivery). School of Biological Sciences: Dr P. Denny [HUB leader](parasitology, assay development, target validation); Dr E. Pohl (drug design, biophysical sciences, protein crystallography); Prof. C. Jahoda (skin biology, 3D skin cell models) and Dr C. Ambler (immunology, skin wound healing).
Collaborator Contribution Expertise as follows: Centre for Immunology and Infection: Prof. J. Mottram [IC](molecular parasitology, target validation, animal models of infection); Prof. P. Kaye (immunology, parasitology, vaccine development, computational modelling); Dr P. Walrad (molecular parasitology, RNA biology); Department of Chemistry: Prof. T. Wilkinson (protein crystallography, structure-based drug design). Department of Electronics: Prof. J. Timmis (Computational immunology, Fault-tolerant swarm robotic systems) SimOmics (SME spin out; Evidence based simulation tools for drug discovery). Organisation of the 2nd advanced course in genetic manipulation of parasitic protozoa to be held in July 2018.
Impact None yet
Start Year 2017
 
Description Article A very unpleasant kiss, Microbiologist 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Article for the Microbiologist, the magazine of the Society for General Microbiology: A very unpleasant 'kiss'. Microbiologist 18(4): 20-21. ISSN/ISBN: 1479-2699
Year(s) Of Engagement Activity 2017
URL https://issuu.com/societyforappliedmicrobiology/docs/web_version_microbio_dec_2017
 
Description Article for Durham University alumni 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 written for Dunelm Magazine (the Durham Alumni publication)
Year(s) Of Engagement Activity 2018