Structural biologist’s journey to inspire

Dr Lizelle Lubbe, a postdoctoral research fellow in structural biology at the University of Cape Town (UCT), hopes that her academic journey and research will help inspire other young Africans to pursue a career in science.

Structural biology is the study of protein structures using physics-based techniques such as X-ray crystallography and cryo-electron microscopy, often at synchrotron radiation facilities abroad. These structures provide vital insight into how a protein performs its biological function or causes disease, and how therapies can be designed.

“I find it very rewarding and motivating to know that, even if I am working behind the scenes and not directly in contact with patients, my research has the potential to yield new therapies and improve their lives,” said Dr Lubbe.

“I hope that this will serve as an inspiration for young scientists to dream big and imagine how they can contribute to the eradication of other diseases in Africa.”

Lubbe’s research focuses on determining the structure of a blood-pressure-regulating protein called angiotensin-converting enzyme (ACE) to guide the design of antihypertensive drugs. While existing therapies are effective, Lubbe believes that their safety should be improved because some patients experience life-threatening swelling below the skin surface, which could obstruct breathing.

Another reason for young people to consider structural biology, which isn’t widely studied in Africa, is that the discipline is currently at the forefront of the fight against COVID-19, where researchers are studying the interaction of the SARS-CoV-2 spike with a protein related to ACE.

“I hope that this will serve as an inspiration for young scientists to dream big and imagine how they can contribute to the eradication of other diseases in Africa,” said Lubbe.

Searching for clues

Lubbe credits her parents with sparking her interest in what would eventually become her field of study and work. From her mechanical engineer father, her curiosity about knowing “exactly how things work” was nurtured; from her mother’s recollections as a microbiologist prior to Lubbe’s birth, a flame was ignited to find out how “molecular machines, such as proteins, work within our bodies to carry out key biological functions”.

Despite her parents not being able to afford her tuition and textbooks, Lubbe persisted. She took out a student loan and enrolled for a BSc in Biochemistry at the University of Pretoria in 2009.

During her undergraduate years, Lubbe became intrigued by proteins and how they can be targeted to treat disease. She was drawn to UCT because of Professor Edward Sturrock, the head of the Department of Integrative Biomedical Sciences, and his research on designing novel drugs to target a blood-pressure-regulating protein for the treatment of hypertension (or high blood pressure) and heart disease.

“ I find it truly amazing that we can see the atoms responsible for causing debilitating symptoms in patients.”

Under Professor Sturrock’s supervision, Lubbe completed her BSc (Med)(Hons) in Medical Biochemistry in 2012. During that year, she was also exposed to a large variety of disciplines within the biomedical field, one of which was structural biology.

She continued her PhD research in Sturrock’s laboratory and was this time co-supervised by Professor Trevor Sewell from UCT’s Aaron Klug Centre for Imaging and Analysis. Lubbe described Professor Sewell as an expert in structural biology and credits his mentorship as having enabled her to branch into the discipline.

“I find it truly amazing that we can see the atoms responsible for causing debilitating symptoms in patients and am fascinated by structural biology,” she said.

She explained that her work feels “a bit like sleuthing at times”, as she searches for clues within a protein structure to understand how it might move to perform its function.

“This can require you to stretch your imagination a bit, and I have come to realise that science is much more creative than I imagined during high school.”

Golden opportunity

While completing her PhD thesis in 2018, Lubbe was offered a “golden opportunity” to join the Global Challenges Research Fund Synchrotron Techniques for African Research and Technology (GCRF START) programme as a postdoctoral research fellow. The programme is funded through the United Kingdom’s (UK) Science and Technology Facilities Council through the GCRF.

“It has been very challenging to fund 10 years of tertiary study myself … I only managed by securing a student loan and various bursaries,” Lubbe explained.

“GCRF START is a revolutionary project which has unlocked growth in Africa and allowed us to leapfrog the traditional challenges.”

The grant from GCRF START was a “godsend” because it meant that she could start repaying her student loan by doing the work she loves. However, her “mountain of debt” is not yet cleared due to the high cost of living in Cape Town.

“GCRF START is a revolutionary project which has unlocked growth in Africa and allowed us to leapfrog the traditional challenges like [the] lack of funding for consumables, access to infrastructure and access to training,” said Lubbe.

She added that it has provided her with the opportunity to go abroad and collect data on sophisticated instruments at Diamond Light Source, the UK’s national synchrotron science facility. She has also attended numerous workshops where she’s received training from experts in the field, thanks to GCRF START.

“It’s very exciting to be in structural biology right now [as] new methods, instruments and software are … making huge strides in pushing the limits of the details we can observe, especially in the field of cryo-electron microscopy, which has only recently become available at UCT at an internationally competitive level,” said Lubbe, who is now conducting research in collaboration with Sturrock, Sewell and Dr Jeremy Woodward from UCT’s Electron Microscope Unit.

For this reason, she explained that keeping in contact with other researchers and staying abreast of new developments are crucial, prompting Lubbe and her peers to start a collaborative network of structural biologists in Africa and the UK. A large proportion of the South African group within the network are women, including UCT’s Dr Lauren Arendse, Sylva Schwager, Lynn Wambua, Naadia van der Bergh, Melissa Marx, Lenye Dlamini, Rani Wiswedel and Professor Virna Leaner, the head of the Division of Medical Biochemistry and Structural Biology at UCT.

The next generation

For Lubbe, scientists must engage with the public – a key part of ensuring gender diversity and growth in the field. By engaging, scientists can uplift communities in need and inspire the next generation.

“It is especially important for us to challenge gender biases and serve as role models so that more women and girls will consider careers in science.”

“It is especially important for us to challenge gender biases and serve as role models so that more women and girls will consider careers in science,” said Lubbe.

“I believe that if you are curious, dream big and have support from inspiring mentors, you can achieve anything that you set your mind to.”

Lubbe added that the GCRF START grant has demonstrated that, despite the challenges facing the continent, such as a lack of resources, it is possible for Africans to perform research that is on par with that of international laboratories and that will improve healthcare.

She credits the grant as having positively impacted the size of the structural biology community in Africa, which has grown substantially since the launch.

“And we have made remarkable discoveries,” she added.

An increase in trained structural biologists means more capacity to design therapies for treatment of numerous diseases prevalent in Africa. This is why Lubbe is actively involved in a collaborative outreach programme between GCRF START and the Keiskamma Art Project, which aims to make the output of the scientists more accessible to the general public through art.

“It is important to broadcast the success of GCRF START through outreach so that people see its long-term value and stem the ‘brain drain’ from Africa,” said Lubbe.