For Ben Clifton, who recently finished his PhD at the Research School of Chemistry, solute-binding proteins has always been an area of interest. The latest student to finish a PhD on the Rod Rickards scholarship, Ben has a long history of researching these proteins at RSC.
“My honours and PhD research focussed on a family of proteins called solute-binding proteins (SBPs),” Ben explains. “We initially became interested in SBPs because they can be used to engineer fluorescent sensors for detecting specific molecules.”
Ben studied a Bachelor of Philosophy — a research intensive program — at the ANU before completing his honours at RSC.
“The goal of my honours project was to reconstruct extinct SBPs to make them into fluorescent sensors for neurotransmitters, which we could then use to learn more about the distribution of these neurotransmitters in different parts of the brain over time, and thus better understand how they contribute to brain function.”
With his research from his honours published in Protein Science, Ben was offered the Rod Rickards Scholarship. This Scholarship named after one of the founders of RSC, Rod Rickards, is given each year to one of the top students in either biological or organic chemistry. For Ben it allowed him to continue his research into SBPs as a PhD.
“My PhD work also looked at SBPs, but we ended up focussing on their evolution rather than the practical applications,” Ben explains.
This turn toward a focus on their evolution was due to a realisation that this understanding can have broader implications.
“SBPs turned out to be useful for investigating the general principles of protein evolution because of their functional diversity. They have evolved to perform a lot of different functions, so there’s many interesting examples of protein evolution to choose from.”
The other benefit SBPs provided was an ease of research process.
“SBPs are exceptionally easy to produce, so you can do experiments that wouldn’t be practical with other types of proteins.”
“The main process I used is called ancestral protein reconstruction, which allows you to reconstruct extinct proteins. If you take a bacterium, for example, reproducing over many generations, the DNA of its descendants will gradually acquire mutations, but will still resemble and retain traces of the original, ancestral DNA.”
“So, if we know the DNA sequences of enough descendants, we can work backwards and find out the statistically likely DNA sequence of their extinct ancestor. It’s then pretty simple to make the ancestral DNA in the lab and use that to make the corresponding ancestral protein. From there, we can directly compare the ancestral protein with the descendant proteins to see directly how evolution has changed the properties of the protein.”
In doing this work Ben made some important findings.
“The first major outcome from my work is that I found evidence for the importance of protein motion and flexibility in the evolution of new functions. This had been a popular hypothesis in the field of protein evolution for the past decade or so, but the evidence for it was mostly indirect. Our work provided a concrete example, from nature, where protein flexibility enabled the evolution of a new function.
“To be more specific, we were able to take a snapshot of an ancestral protein using X-ray crystallography, which caught the protein switching between two structures that could interact with two different molecules–this ability eventually allowed the protein, later in its evolutionary history, to specialize and interact with one specific molecule.”
Importantly for Ben his research highlighted the value of research not just focused on practical outcomes, but also on understanding the different chemical elements that make up our world.
“SBPs have some specific practical applications. But understanding the general principles of protein evolution is also important because the better we understand how proteins have acquired useful functions through evolution, the better we will be able to mimic those strategies to engineer proteins for our own purposes, whether that’s degrading environmental toxins or synthesising new drugs, or any other application that proteins have in the biotechnology or pharmaceutical industries.”
Reflecting on his time at RSC Ben emphasised the importance of the financial support provided by the scholarship in his ability to complete his work.
“I wouldn’t have been able to get a PhD any other way,” he explains. “It allowed me to get involved in research I was very much interested in. Being at RSC gives you a lot of opportunities in terms of collaborating with other researchers travel and learning new skills.”
Ben emphasised in particular the unique environment available at RSC.
“I found the research group I was in in particular was very supportive environment. Everyone is looking out for each other and helping out with each other’s research. It’s just exciting to be part of the RSC when there’s so much more research going on around.”
What’s next? Ben isn’t sure, but there are plenty of opportunities available.
“I haven’t decided what I’m going to do next. I’m still trying to decide how best to use the skills and experience acquired during my PhD. I’m strongly considering teaching science–I think it would be a good way to keep learning and using science while making a direct impact on people.”
Either way its clear that his time at RSC, and the support he received from the Rod Rickards Scholarship, has set him up for a strong future.