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The gene editing workshops tackling invisible diseases

by Guest Author on 3 May 2019

Recently, an international group of researchers met in Kolkata, India, for a workshop ran by the Global Network for Neglected Tropical Diseases. Here, Project Officer Mags Leighton explains how the network – and revolutionary gene editing technology – is creating new ways to tackle two neglected diseases.

Kolkata workshop attendees. Image copyright: Prof Nahid Ali.

Millions of people worldwide are infected by neglected tropical diseases (NTDs). The Global Burden of Disease Study 2017 revealed that just two of these – Chagas disease and leishmaniasis – together infect over 10 million people, causing an estimated 16,000 deaths and 321,000 ‘years lost to disability’.

Yet these figures are likely to be vast underestimates. Infection rates are highest in remote areas, where cases are often misdiagnosed and under-reported. Currently, we lack adequate treatments for these two diseases – the Global Network for Neglected Tropical Diseases aims to change this.

Chagas disease is spread by insects (top left) which often bite patients around the eyes, causing local swelling (top right). The parasites (Trypanosoma cruzi, bottom left) stay in the blood during the acute phase of the infection, but then can ‘hide’ in the body as a chronic disease, causing damage resulting later in heart failure (bottom right) or gastrointestinal problems. Image copyright: Wikimedia Commons.

Our network brings together 400 researchers and academics from 13 institutes around the world. We’re working together towards the common goal of delivering the scientific advances that will drive the creation of new therapies for leishmaniasis and Chagas disease.

The revolutionary gene editing technology CRISPR-Cas9 is a game-changer for understanding the trypanosome parasites behind Chagas disease and leishmaniasis. But currently, there’s a shortage of scientists in the affected countries able to apply this technology to these organisms.

This is why, as well as fostering collaborative research to develop the next generation of therapeutics, the network is also providing interdisciplinary, state-of-the-art training to early career researchers from South America, South Asia and the UK.

In March, 28 researchers from different countries came together for one of our workshops – in Kolkata, India – to discover how to apply CRISPR to gain new insights into the complex genetic picture of these disease-causing parasites.

‘Invisible’ diseases: a global problem

Both diseases might initially be symptom-free, persisting ‘silently’ for years, before revealing themselves through life-threatening conditions like heart disease and liver failure. But even when symptoms are less serious, their effects can have devastating social consequences.

Leishmania parasites are spread by sandflies (Phlebotomus spp, top left) and infect white blood cells (below left). Different forms of the disease target either the internal organs (top right) which is lethal if untreated, or skin (bottom right) causing disfiguring scars. Image copyright: Wikimedia Commons.

For example, in some leishmaniasis cases, disfiguring scars exclude sufferers from education, marriage and employment.

Current treatments have limited efficacy, are toxic and can themselves be lethal. Even if these medicines were free, enduring such risks and side effects is too high a price for most patients.

Training the new pioneers

The need for safe treatments, and the global shortage of suitably skilled researchers, inspired us at Durham University to establish a Global Network for Neglected Tropical Diseases.

Our mission is to find new drug targets for Chagas disease and leishmaniasis, and equip the next generation of researchers, in endemic countries, with the skills and molecular tools needed to face these ongoing public health challenges.

Identifying suitable drug targets in trypanosome parasites is extremely difficult. To survive inside their insect and mammal hosts, trypanosome parasites change their internal molecular machinery. Because of these changes, most standard genetic techniques simply don’t work. CRIPSR overcomes many of the challenges that prevent the use of other genetic techniques in these parasites, to allow researchers to rapidly and precisely tag, edit or remove specific genes

The network’s first workshop in Rio de Janeiro trained 18 students, from Brazil, Argentina, Uruguay and the UK, to use CRISPR to analyse two parasites – Trypanosoma cruzi and Leishmania spp. – which are endemic in South America.

Workshop organiser Professor Ana Paula Lima, from the Federal University of Rio de Janeiro, believes CRISPR will transform parasitology: “I’ve seen so many enthusiastic young researchers become frustrated at their slow progress with these organisms. CRIPSR makes it possible to investigate a whole family of parasite genes at once, or all the stages of a biochemical process. This changes everything!”

The parasite Leishmania was the sole focus at the recent Kolkata workshop due to the widespread prevalence of leishmaniasis across Asia. Most of the 28 participating students were from research institutions around India, but others came from Saudi Arabia, Brazil, Germany and the UK.

Students attending the Kolkata workshop received hands-on training from expert staff (below, right) and networking opportunities during breaks (above left). Image copyright: Sarah Smith.

Organiser Professor Jeremy Mottram, from the University of York, reflects on the workshop: “The workshop in Kolkata provided theoretical and hands-on training in Leishmania gene manipulation, allowing students to extend the technology into their own research programmes. The success of the workshops in Rio de Janeiro and Kolkata are inspiring us to hold further training for researchers from developing countries.”

A new cohort of enthusiasm

New technologies typically take a long time to become widely adopted. The network’s CRISPR workshops are transforming this slow process for trypanosomes researchers, by providing practical skills combined with direct access to world-leading, expert advice.

Since the first workshop in Rio, several students report that their training has changed the direction of their careers and transformed the way they approach their research. Many have shared their knowledge with others at their home institutions. The cohort keep in touch via social media, exchanging ideas and forming new collaborations.

We believe that the legacy from the Kolkata workshop will prove similarly transformative. Attendee Sarah Smith, from Durham University, commented that her training in Kolkata was “…invaluable both for scientific reasons, and as an opportunity to meet other young researchers and academics and hear about the fascinating parasitology research elsewhere in the NTD Network”.

These workshops are providing career-changing CRISPR expertise to researchers around the globe. But more importantly, they’re driving forward research that aims to improve the lives of millions at risk from Chagas disease and leishmaniasis.

The network is funded as part of a UKRI Global Challenges Research Fund (GCRF) Growing Research Capability award (MR/P027989/1), headed by Professor Graham Sandford at Durham University.

Comments

Well done, its about time people were made more aware of how unknown disease is dealt with… I believe that doctors should give radem checks, as alot of people today are allergic to allot of different foods and colours. I have suffered for 3 months of headaches myself.
I now realise I. M allergic to sweeteners often added to drinks instead of sugar and ibrufen… But also arthritis in the knees and back, but I do live in England, which is cold and damp alot of the time, I also believe that air conditioning just makes breathing worse, especially in confined spaces like long aircraft flights.
My dearly daparted love died of cancer, which I. M sure he picked up sitting next to a old nan that coughed most of the flight from Gatwick to Barbados, as when we eventually boarded a cruise ship, he had a fever for 2 days, but refused to see a doctor as it would have cost him a £80 surcharge…
So good luck with your research and may you find some natural cures…
I take garlic and enjoy cooking with garlic as I find it helps to cure any breathing problems or colds..
I also take turmeric black pepper lemon juice and honey in hot water, as I find it keeps the pain of arthritis at bay… Yours sincerely
Miss S C Smith

author avatar by Susan carol smith on 06-May-2019 00:47

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