Crystals of a DNA repair protein bound to DNA Credit: Bernard O’Hara and Renos Savva. Wellcome Images

Catalysts and cancer: from energy cells to cancer research

30 August 2016

Science today is an interestingly fluid field, where new ideas and technologies blend with theory to push boundaries and address growing questions. Dr Edmund Tse’s work epitomises this movement, but with an added twist of going back to basics.

Tse’s doctoral work centered on fuel cells, energy conversion devices in fuel that create electrical energy. These devices are more efficient than heat engines, such as the ones in cars, and are thought to be future choice of transportation. 

His research took a basic science approach rather than with an eye for industrial-scale markets, looking to nature to see how it does things. 

For fuel cells to work properly, they need specific catalysts for certain reactions. Enzymes in nature like laccase in fungi, categorised as blue copper oxidase, are powerful catalysts at certain pHs and temperatures. Mimicking the active side of this enzyme as a catalyst on a smaller scale for higher power density, Tse experimented on expanding natural models for better fuel cells.

Looking to nature

In his postgraduate fellowship at Caltech, Tse has taken a new direction towards electron transfer in cancer treatment and prevention, but again with an emphasis on improving on natural processes. The lab’s current research pursues the idea that electrons can be transferred across DNA, which has the potential to serve many purposes, including DNA acting as a medium for protons to talk to each other. 

Dr Edmund Tse

There are many ways for this to happen in biology through signaling pathways, but these typically require a third-party messenger to relay the message, which means there are errors in transmission or messages not being relayed fast enough. Some proteins can work alone, but usually have to work together for something to happen. 

Teams of proteins routinely search for and repair DNA damage in the body, and if this damage is not fixed in time or properly, the door is left open to cancer or genomic instability.

Studying how these proteins search for and repair damage can yield interesting insights into how natural biological mechanisms can be protected or enhanced to prevent cancer. 

The proteins form iron- redox-active (reduction and oxidation) sulfate clusters, so hypothetically, one protein will bind to DNA (naturally oxidised), another reduced protein will bind at the other end, and an electron transfer event will happen across the DNA molecule. The sensing mechanism is thought to be when the oxidised protein becomes reduced and vice versa, and the reduced protein pops off the DNA. 

In the case of a DNA defect, the electron transfer between the proteins at either end is disrupted, so the proteins move along the molecule to search for errors. Tse equates this to making a telephone call: if the call successfully goes through, the line is fine, if not, you know to call the repairman instead. Very few proteins search a huge number of genomes every day, and have to do it efficiently because overlooked defects have serious downstream effects.

Insights into cancer

Cancer research deals heavily with better drugs, especially with the molecular targeting or the new idea of big antibodies attached to T-cells, or earlier detection and diagnostics, as cancer becomes harder to treat in later stages. Tse is drawn to the basic science angle which focuses on building more fundamental knowledge for curing cancer and diseases. 

Basic science research often doesn’t get as much attention in favor of metrics and numbers that say if something works, Tse says. However, understanding delicate processes, what knobs to turn or what to think of for certain outcomes, is fundamentally very important for the kinds of doors that modern research is looking for.

Understanding the actual mechanisms would allow researchers to make headway on testing and curing through enhancing the body’s ability to prevent and repair itself. 

His lab includes people working on early detection, drugs, devices for early diagnostics, and proteins on cancer-causing mutations, collaborating with hospitals and other departments. Tse is currently working on in vitro experiments because of his interest in the technical details of how different mechanisms in the body work, but notes that all of these different components communicate for more effective research.

From energy to medicine

Transitioning from fuel cell to cancer research is an unusual one, and Tse laughs that he’s working on a better answer, given how many times he gets the question. There is no single reason, and the major change in direction hasn’t been easy. Almost all the experiments are new; while previous research involved basic knowledge of DNA and protons, Tse had never made a functional model or delved into the technical side. 

“I wanted to really know these essential structures, not just look and assume,” he explains. “I want to know why a body chose this protein and why it’s made, why it’s useful.” 

Personal reasons also influenced his decision. As people close to Tse were diagnosed with cancer, his consciousness of its growing impact sparked his scientific mind too. “I used to think that the energy crisis was a more universal problem than cancer, about all of us rather than something that affected a few. But cancer doesn’t just torture the patient—families, friends, and communities are affected directly and indirectly because of a disease we can’t control, are struggling to catch up with and understand, and is always changing.” 

The research focus shift also involves working more on electron transfer from his previous proton transfer study, which he hopes will help in furthering his understanding of comprehensive systems. A more complete understanding of the mechanisms is key to coming up with proactive solutions, such as enhancing natural processes or testing how our body is doing before needing to go into defensive mode.

Tse’s explorations have deepened his interest in applied chemistry, particularly in understanding cancer and solving the energy crisis. Contrary to how popular culture tends to categorise scientific researchers, Tse credits extensive reading, thinking about what we can do to change the world, and his surroundings as the driving force behind his scientific curiosity. 

“Catalysts are all around us, scientific or personal,” he says, “Many chemical and biological reactions are started to find better yield, performance, selectivity; but it’s equally important to study what it means, or what impact it would have, as well as what it can do.”

Dr Edmund Tse attended the University of Virginia for his undergraduate study in chemistry, specialising in material science. He received his PhD from the University of Illinois- Urbana Champaign in organic chemistry and catalysis, and is currently undertaking postdoctoral research at the California Institute of Technology. Tse is a 2016 Croucher fellow, and was awarded a Croucher scholarship in 2013. 

To view Dr Tse's personal Croucher profile, please click here.