Q: What made you decide to major in chemistry?
EW: My dad’s a physicist. I grew up spending time thinking about `here’s the natural world, what’s going on’ kind of questions-so I love science. And I just really like the molecular level understanding, trying to really understand. In college, I loved organic chemistry because once you understand what’s happening, it can be predictive. I love being able to do the experiments, have a prediction, go in test it and ask “Does that make sense?”.
Q: What made you transition to biomolecular chemistry?
EW: I’ve always really been interested in living systems and trying to sort out what’s happening in these complex systems. I had always hoped to get to the part in my Ph.D. (working with quinone methides) where we’d learned enough to go in vivo and test some of our theories. But like so often happens in science, sometimes you find that you really don’t understand things that well or you get drawn in different paths-so I wanted to do something more biological after focusing on small molecules.
Q: Did you ever want to be anything else?
EW: Actually, when I was growing up I wanted to be a wildlife biologist.
EW: Yeah, live out in the wild and count the wolves and watch their migration patterns… But then I realized I didn’t really like the cold that much and living out in a tent with things that could eat me makes me a little nervous so I ran for the lab instead. I think it worked out a lot better.
Q: And you have, like, you know…plumbing
EW: Yeah, (laughs) that was another thing.
Q: What research does your lab focus on?
EW: My lab does protein chemistry. We’re interested in understanding how proteins work, thinking about them as complex chemical systems rather than as the normal circles and pac-men that we often see.
The two general interests in the lab are heme proteins and nucleotide signaling. We have some proteins that are heme proteins and some proteins that are involved in nucleotide signaling and at the intersection are a group of proteins that have both heme domains and do nucleotide chemistry. We’re looking at cyclic nucleotide signaling in bacteria and some potentially new cyclic nucleotides that are involved in pathways in mammals.
We’re also interested in heme proteins and how protein scaffolds tune the electronics and the reactivity of the heme itself. A lot of heme proteins use protoporphyrin IX, although there are some other porphyrins, but you can take protoporphyrin IX and do chemistry with oxygen, like peroxidases and P450 enzymes. And you can also use the same porphyrin to do reversible ligand binding for oxygen delivery or for sensing. So organisms can actually sense gases, binding very low concentrations of ligand so that it causes a downstream change in the organism.
Q: And this variation in activity is dependent on the protein structure?
EW: Yes, the scaffold itself. So you can change the redox potential widely from around -400 mV to around 380 mV. That’s a huge change. You can change the type of reaction; you can change if you can do electron transfer with most of the biologically available oxidants and reductants. And so it can changes just about everything. And right now, our understanding of that is still pretty poor. There’s a huge amount of work that’s been done on the globins. I think there are probably at least 150 mutants of myoglobin that have been published, but it’s still not very predictive and we can’t always apply it to other heme proteins. So, like most protein engineering or protein chemistry, we don’t have a lot of predictive power to suggest how mutations will affect the heme.
Q: Which chemist do you wish you had an opportunity to meet?
EW: Rosalind Franklin and Hans Fischer.
Q: Why them?
Rosalind Franklin has a fascinating story. The work she was doing was still in a time when it was not necessarily expected that many women did their own science. She was clearly brilliant and she figured out most of the structure of DNA before Watson and Crick. The reason Watson and Crick got the structure was by looking at her data. Unfortunately she died before the Nobel Prize was given and they don’t give it posthumously. I think she would be fascinating to talk to and to hear her story.
Hans Fischer was the first to discover chlorophyll and heme and he was the first one to figure out what these pigments were and to synthesize them. I think it’s really interesting to think of how do you go about, at the time (the 1920’s), saying `I’m going to isolate this colored compound’ and then how do you go about with the techniques then available figuring out what all is in there? I think it would be really interesting to hear how the field got started from the guy that started the field!