From medicinal chemist to protein crystallographer, Dr Anton Hamann has made remarkable strides in structural biology despite many challenges. These achievements he attributes to new doors of opportunity which have opened as a result of GCRF START grant funding for his role as a Post-doctoral Research Fellow at Stellenbosch University, South Africa – a role which has changed his life and career in many ways. Although possessing “no previous experience” (as he puts it) in the particular techniques and skills required, Anton has not only retrained into a new field of science in a short space of time, but he has also learnt world-class techniques scarce in Africa, and now develops small and novel molecule inhibitors to combat diseases. Here is his inspiring story in his own words….
My love for science and medicine
My name is Anton Hamann and I grew up on the outskirts of Cape Town, in the Western Cape of South Africa. I was diagnosed with severe hearing loss in both ears with no possibility of recovering the loss. Despite this, from a very young age, I enjoyed science and building contraptions. I was also a bookworm and always enjoyed visiting the local library. My high school science teacher was extremely passionate in chemistry and motivated me to pursue a degree in chemistry. As a result, I decided to pursue a career in science, starting with a BSc degree in Chemical Biology at the University of Stellenbosch. After that, I started with my postgraduate studies (BSc Honours, MSc and PhD) with organic chemistry as my discipline.
I was always fascinated in medicine and how it affects our bodies and staves off diseases. It was questions like – What molecules are involved and how do these molecules change the biology in our bodies? How can we use these molecules to combat diseases? Can we cure these diseases with better molecules? What are these molecules? – that intrigued me.
This prompted me to do research in the field of medicinal chemistry which is a multi-functional field with various applications in drug discovery, drug design, synthetic chemistry, and protein molecular modelling. During my MSc and PhD, I focused on developing drugs with better medicinal properties for the treatment of malaria and Alzheimer’s disease. Over the course of time, I have synthesised several molecules that have the potential to be further developed into medicinal drugs for malaria and Alzheimer’s disease. This has resulted in two publications for my work in malaria (South African Journal of Chemistry, 2013, 66, 231-236 and Bioorganic & Medicinal Chemistry Letters, 2014, 24, 5466-5469) and we are currently in the process of publishing the Alzheimer’s disease results in a peer reviewed journal.
Re-training as a protein crystallographer
After my PhD, I decided to carry on with my research in the field of medicinal chemistry but was looking for a new challenge. This is when I joined Prof. Erick Strauss’ research team as a post-doc to explore the possibilities of developing novel antibiotics for Staphylococcus aureus. This is also where I heard about the GCRF START grant for the first time.
Although GCRF START’s life sciences focus is mainly structural biology, a field in which I possessed no previous experience, I was determined to learn as much as possible and be retrained as a protein crystallographer. This is where the START grant made a significant impact on me, not only fully funding my role as a post-doc but also giving me opportunities to attend conferences and workshops in South Africa and UK, and to hone my skills as a protein crystallographer. As I’ve progressed during my post-doc, I have become a better medicinal chemist with the new skills that I have developed in the field of structural biology thanks to the opportunities provided by the GCRF START grant.
The GCRF START grant has given me an incredible opportunity to visit XChem twice for two weeks in total at the UK’s national synchrotron, Diamond Light Source (Diamond), to carry out X-ray crystallographic fragment screening experiments. I’ve gained valuable experiences from Dr Romain Talon and Dr Alice Douangamath and these visits also introduced me to a new field of high-throughput screening where the workflow is almost fully automated. I’ve had access to Diamond’s state-of-the-art equipment including the I04-1 beamline. During this time, I’ve had the opportunity to soak my protein crystals with hundreds of different fragments to identify potential small molecules that bind to the enzyme. These molecules can then be expanded into larger molecules with higher potency and act as antibiotics for Staphylococcus aureus.
To date I’ve used the I03, I04 and I04-1 beamlines at Diamond to obtain diffraction data of my Staphylococcus aureus protein crystals which was extremely valuable to my research. I have also attended a CCP4 (Collaborative Computational Project Number 4) workshop in York in the UK, where I learned how to process the diffraction data to solve the crystal structures. GCRF START is one of the CCP4 workshop partners.
Another benefit of the GCRF START grant has been the fruitful collaborations and relationships that I have built with other South African and British structural biologists who have significantly aided my career progression. In addition, I have learned valuable tips and skills from Romain and Alice at Diamond. They gave me insights on how to achieve optimal crystals and what to do if your proteins do not crystallise. They have been incredible in assisting me with the XChem project.
Commenting on Anton’s achievements and the support of the GCRF START grant, Prof. Erick Strauss said,
“I’ve always personally been of the opinion – and this is especially relevant in the South African context – that a scientist with multiple skill sets and the ability to transition easily between fields is more likely to make a deep impact. It was with this in mind that I was really happy to welcome Anton into my group: as a skilled synthetic chemist I was certain that he would be more than able to take on protein crystallography to bridge the chemistry/biology divide. And without the GCRF START grant, this would not have been possible – we are extremely thankful for this support.”
Acknowledgements
I would like to thank Prof. Erick Strauss, who is a GCRF START Co-Investigator, for taking a gamble on someone like me who is an organic chemist and not a biochemist! The effort he was willing to put into me and this project is highly appreciated. I couldn’t have asked for a more invested supervisor. I am also grateful to my lab mates, Dr Blake Balcomb (GCRF START-funded Post-doctoral Research Fellow) and Konrad Mostert, for teaching me the nuts and bolts of protein chemistry. I am also thankful to Dr Carmien Tolmie (previously a GCRF START-funded Post-doctoral Research Fellow) and the other GCRF START Co-Investigators, Prof. Trevor Sewell, and Prof. Wolf-Dieter Schubert for their work behind the screen to keep things running smoothly. Lastly, a big thank you to the people at Diamond for making this a reality.
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