African Physics Newsletter

The START of Structural Biophysics in Africa Threatened by COVID-19

A new programme to enhance capacity in structural biology in Africa faces the urgencies of COVID-19.

The COVID-19 disaster has resoundingly demonstrated the power of today’s visualization technology in leading to an understanding of how the disease works at an atomic level and how these insights can be used to design medicines and vaccines [1, 2, 3, 4 , 5 , 6, 7]. Scientists based in Africa do not have local resources that enable them to participate in this work that is both fascinating and fundamental for the survival of society as we know it.

Not having a robust foundation in structural biophysics in Africa makes us totally dependent on research done abroad and puts us in peril of not being able to respond in a properly informed manner not only to the threat of new diseases but to the older ones like TB, malaria, AIDS, heart disease, diabetes, etc.

A struggle to find resources

Biophysicists throughout Africa have long been aware of how they could potentially contribute to alleviating the disease burden in Africa but have struggled to find resources to realize their ideas. The award of the Global Challenges Research Fund Synchrotron Techniques for African Research and Technology (GCRF-START) grant in 2018 was a breakthrough in many ways.

The grant funded the development of the three areas of energy materials, catalysis, and rational drug design. The intention of the latter was to design medicines based on a knowledge of the atomic structures of the target protein molecules.

Training young African scientists

The grant was aimed at training young African scientists to use synchrotrons and the associated facilities to accelerate their own research. The biophysics component was structured around 9 co-investigators from the Universities of Cape Town (UCT), Stellenbosch, Witwatersrand, Free State, North West, Pretoria, and the National Institute for Communicable Diseases.

Each co-investigator took responsibility for hiring a post-doctoral research associate who was given a generous research budget and a travel allowance. In addition to the post-docs, a “Centre of Excellence” was established at UCT that was responsible for enabling the post-docs to execute the full structural biology workflow and thus fill in the links that were missing at their host institutions.

Workshops in Africa

The grant also provided a generous allowance for locally held workshops and extended study visits abroad. The biophysicists were quick to get going and organized a number of workshops in Cape Town, Johannesburg, and Pretoria.

The largest Cape Town workshop Biophysics and Structural Biology at Synchrotrons, organized in collaboration with the International Union of Pure and Applied Biophysics (IUPAB), attracted 49 student participants and was conducted by 15 international and 5 local scientists. Many of the presentations were published in Biophysical Reviews (Volume 11), a special edition devoted to Biophysics in Africa.

Cryo-electron microscopy

Among the topics introduced was cryoEM (cryo-electron microscopy), a field that has been revolutionized by modern computer hardware and software and the direct electron detector.

Recent structures of giant macromolecules and viruses determined using this technology routinely approach atomic resolution. The South African community was granted block allocations on both the X-ray crystallography and cryo-electron microscopy beamlines at the Diamond Light Source at Didcot, UK.

A number of significant papers

Enthusiastic use of these facilities has resulted in a number of significant papers by South African authors, including the very first description of a nitrilase enzyme by Drs. Mulelu and Woodward at UCT. These enzymes are key to the manufacture of both commodity chemicals and novel medicines.

A unique resource at the Diamond Light Source is X-Chem – a facility for visualizing small “molecular fragments” in protein binding pockets. This is being exploited to design novel medicines to treat tuberculosis by Prof. Strauss, Dr. Balcomb, and Dr. Hamman at the University of Stellenbosch.

A cancelled event

The program organized the very first CCP4 workshop in Africa in collaboration with IUPAP to be held on 4 April 2020. CCP4 coordinates and distributes the software for macromolecular structure determination. The organization was a pioneer in the development of open source, community-driven software and has been a powerful driver of the discipline of structural biology.

Substantial sponsorship was secured from the SA National Research Foundation and the International Union of Crystallography as well as CCP4. The event was cancelled at short notice by the level 5 lockdown.

A struggle to maintain momentum

Indeed, the succession of lockdowns has put the brakes on most activities within the program except those related directly to the study of coronavirus. It has been a trying time for the students, post-docs, and co-investigators who have struggled to maintain momentum in spite of the collapse of many of the resources on which they depended.

We are working to establish an infrastructure for remote activities, dependent on dedicated services that are determined to keep running with minimal risk to those operating them.

Urgences opposes long term research

The incredible progress that has been made in establishing structural biology on the African continent remains extremely fragile. Ironically, emergency cuts and delays in science budgets, made in response to the COVID-19 crisis, strike at the very essence of a program that gives Africa the tools to mount a rational, science-based response to the real threat of recurrent novel virus outbreaks.

Trevor Sewell, University of Cape Town, South Africa

This post has first been published in the African Physics Newsletter - © American Physical Society, 2020

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