Kira Weissman tells Joanne Thomson how the genetic engineering of bacteria could lead to new drugs.

Kira Weissman is based at the Department of Pharmaceutical Biotechnology at the University of Saarland, Germany. Her research involves structural and mechanistic studies of modular multienzymes. Kira is a member of the Natural Product Reports editorial board.

 

What inspired you to become a scientist?

My parents are both scientists, so it was almost inevitable that I would be too. I have always been curious about how things worked. I did a few pseudo science experiments when I was a kid, like mixing stuff and seeing how long it took to rot outdoors!

I had a really good mentor in college who got me into the lab and really excited about doing research. Not everything worked of course but, by in large, it was her influence that encouraged me to become an academic.

What projects are you working on at the moment?

We are looking at the way that bacteria make drugs. It turns out that in some cases, the proteins that are responsible are enormously huge and enormously complex. We try to understand the enzymology, that is, how they work on a fundamental level, as well as studying their structural biology. We also try to manipulate the pathways on the genetic level, in order to change the protein structures, and consequently the final products. The overall idea is to make new drug molecules by genetic engineering of bacteria.

What is the trickiest problem you have had to overcome in your research?

I wouldn't say there was one thing. The research is almost a constant challenge. The field as a whole started out really optimistically. If you look at the genetic architecture of the biosynthetic proteins, they appear to be modular - you can divide them easily into functional units. Researchers originally thought that you could just identify a functional unit, swap it with another unit you were interested in and the resulting protein would be different in the way that you wanted. In fact, things are much more complicated than that. A lot of these mixing and matching experiments don't work or produce low yields of the expected products and we really don't understand why yet. Everyone is a bit more sober about the prospects, though we haven't lost our optimism. At the moment, we are really just trying to understand the fundamental enzymology.

What is hot at the moment in chemical biology?

There was a time when people were turning to combinatorial chemistry as a new source for promising small molecule leads, but I think that people are now coming back to natural products. This rediscovery of natural products is exciting for me, because I'm in the business of studying them. I think that people have realised that nature really has done a good job of creating molecular diversity and therefore isolating new natural products and making modifications to their structures is a good place to start for drug discovery.

What is the secret to becoming a successful scientist?

Perseverance and patience because it takes a long time to get anything done. You really have to work at it. The ability to concentrate very hard on one area. Creative thinking - you have to take what you know and put it all together in a new way, something which I believe cannot be taught. As much as you can learn, it doesn't mean that you can come up with novel ideas. And, of course, the ability to communicate with people.

How do you think more women can be encouraged to take up a career in science?

Mentoring is extremely important. I have benefited from mentoring at every stage of my career. There were always scientists more senior than myself who made an effort to promote me - to do everything they could so that I would be successful. People must take it upon themselves to help women, whatever level they are at, to stay in science, to continue to be interested in science, and the earlier the better. And of course, seeing women who are successful makes you believe you can do it.

Which scientist do you most admire and why?

I would have to say it is Peter Leadlay [University of Cambridge]. Not only because I have a strong personal relationship with him but because I think he has real scientific integrity. He does wonderful science and writes beautifully about it. He is also a well-rounded person - there are a lot of other facets to him besides the science. Overall, I find him a very inspiring person to work with.

If you weren't a scientist, what would you do?

There are not many other jobs that I would want to have, to be honest. I think I was always going to be an academic. However, I have become fascinated by languages as I've recently been exposed to more of them as I live in France and work in Germany. So, perhaps I would be a linguist. There are of course other things I wish I were better at, such as music and writing, but I think science is where I was always going to be.