Seeing further: A Brazil-UK collaboration to shine light on the mysteries of parasite cell membranes
“If I have seen further, it has been through standing on the shoulders of giants” (John of Salisbury, 1159).
NTD Network partners and colleagues from Durham, UK and universities from across Sao Paulo state in Brazil gathered this week at Durham University to launch an inter-institutional sister collaboration, investigating transmembrane proteins from neglected tropical diseases (NTDs) and other infectious agents. The FAPESP-SPRINT initiative project is a joint venture between the UK’s Biotechnology and Biological Sciences Research Council (BBSRC) and Brazil’s Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). Membrane proteins hold huge potential as drug targets, yet are poorly understood, this ‘invisibility’ due to the technical challenges of working with these often insoluble proteins. This collaboration, between Durham University, the University of São Paulo (USP) and the Brazilian Biosciences National Laboratory (LNBio), combines the cross-disciplinary expertise from all three institutions. The team plan to develop a suite of tools for characterising the membranes of living cells, equipping us to ‘see further’ in our search for new drug targets for Chagas disease, leishmaniasis and other NTDs.
Today the National Scientific and Technical Research Council (CONICET) in Argentina published an interview with Professor Claudio Pereira on the NTD Network and the role of our Network partners amongst its membership. The Network project is seeking novel drug targets towards solutions for two neglected tropical diseases, Chagas disease and leishmaniasis, alongside forging new industrial collaborations and training early career researchers in the specialist skills needed for this vital work.
Claudio, based at the Instituto de Investigaciones Medicas Alfredo Lanari in Buenos Aires (IDIM, CONICET-BA) is scoping the druggable potential of proteins involved cross-membrane transport of metabolites in Trypanosoma cruzi (causing Chagas disease). Read the interview on the work of Claudio and his team, here.
Our other partners are Professor Julia Cricco at the Institute of Molecular and Cellular Biology of Rosario (IBR, CONICET-UNR), investigating components of heme uptake and biosynthesis, and Professor Guillermo Labadie at the Rosario Institute of Chemistry (IQUIR, CONICET-UNR), investigating naturally-sourced compounds for their potential as novel anti-parasitic drugs.
Guilllermo is co-organising an upcoming Network training workshop in skills for drug discovery, at Mendoza City, Argentina, 2-4 November 2019; bursaries are available to support students to attend. Workshop information is available via our events page.
“Structure is the starting point for understanding any protein!”
Dr Amy Goundry is currently a post-doctoral research associate from the lab of Ana Paula Lima (Federal University of Rio de Janeiro). Amy’s career to date has focussed on one, puzzling protein. “Inhibitor of Serine Peptidase 2” (ISP2), is a protein found in Leishmania parasites, enabling them to infect their mammalian (including human) hosts. Serine peptidases are enzymes with key roles in health and disease, appearing in organisms everywhere from viruses and bacteria to humans – everywhere that is, except in Leishmania. Once a sandfly bite has introduced Leishmania parasites into the body of a mammal host, they must quickly infect white blood cells, and modify the behaviour of these cells, in order to survive. The parasites produce ISP2, which inactivates white blood cell serine peptidases and halts the immune response.
“…but after more than a decade of research, we still don’t know how ISP2 works!”
This puzzle has brought Amy to Durham University for a 5-week secondment with our structural biologists – Dr Ehmke Pohl and the crystallography team.
Cutaneous leishmaniasis (CL) is endemic across most of the Middle East, and is currently expanding into new areas. This August, CL specialists Professor Iqbal Choudhary (Pakistan HUB leader) and Dr Sammer Yousuf, from the International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, journeyed to connect with colleagues from the Network for Neglected Tropical Diseases (NTDs) in Durham and York. Their visit consolidated plans for a training workshop, “New Anti-leishmanial Leads from Natural Sources: Concepts and Approaches” at the ICCBS on 8th-9th November, following the “7th annual Symposium on Molecular Medicine and Drug Research” at the University of Karachi, 4th-7th November. The NTD Network is collaborating with the University of Karachi to support early career researchers (ECRs) from Middle Eastern countries to attend both events.
After a long wait, a piece of vital equipment, the “CFX96 Touch™ Real-Time PCR Detection System”, co-funded by the Global Network for Neglected Tropical Diseases (NTDs) and the University of Karachi, has now arrived at the International Center for Chemical and Biological Sciences (ICCBS). The machine (a white box with screen – visible in the right of the picture) now enables Network members Iqbal Choudhary, Sammer Yousuf and the Karachi team to use the polymerase chain reaction technique (PCR) DNA amplifying technology to identify genetic variations between strains of Leishmania parasites, causing leishmaniasis. This purchase is also a behind-the-scenes administrative triumph for international collaboration, highlighting some of the bureaucratic difficulties we navigate with our NTD Network colleagues in developing countries.
The second Centre for Global Infectious Diseases (CGID) annual meeting, a joint venture Durham University and the University of Newcastle, took place today at the Newcastle Medical School, hosted by our colleagues from the Newcastle University Fungal Research team. This year’s programme showcased some of the engaging research into global infections that takes place across the northeast UK, and gave particular emphasis to early career researchers working on globally-significant diseases, many of which impact developing countries. … Continue reading
This March, 2019, a diverse group of 28 students gathered at Kolkata’s Indian Institute for Chemical Biology, for a workshop providing practical skills in genetic manipulation of Leishmania parasites using CRISPR-Cas9 technology. These new skills will transform their careers, and in time may improve the lives of people affected by leishmaniasis, a global problem which poses a risk to the lives of millions of people in India and Pakistan alone.
Prior to delivering a workshop at the University of São Paolo (USP) Ribeirão Preto campus, UK Network members Patrick Steel, Paul Denny, Ehmke Pohl and colleagues from USP and Durham University, spent a day exploring. The Serra da Canastra national park in Minas Gerais, the origin of the São Francisco river, is home to a tropical and scrubby forest, known to these scientists as USP professor Noberto Lopes’ “chemical hunting ground”. The workshop, “Development and evaluation of bioactive compounds” (March 25th-29th 2019; funded by Brazil’s Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ‘SPRINT’ initiative), equipped ~40 Brazilian postgraduate students with skills to source novel chemicals from plants, fungi and animals. USP’s natural products library already holds many naturally-sourced compounds new to science, but more are needed – as leads for new medicines to treat the Neglected Tropical Diseases (NTDs) affecting Brazil and other developing countries. On this hot day, the team veer off a well-trodden path to go exploring in the forest, taking in spectacular waterfalls and an impromptu swim.