Organic superglues, disease treatments and better food flavourings

Organic superglues, disease treatments and better food flavourings: these are some of the projects where synthetic organic chemist Carol Taylor employs her skills.

Carol Taylor calls herself an “architect, engineer and builder”. The Associate Professor of Chemistry at Massey University, New Zealand designs and makes molecules which she hopes will ultimately enable others to make advances in treating diseases, and developing new surgical products.

Providing the “atomic infrastructure” is the speciality of Dr Taylor’s seven-strong team.

“A lot of biologists and biochemists are full of ideas but they can’t get their hands on the molecules to answer the really interesting questions. What we can contribute is the ability to make things, and I love making things,” Dr Taylor says.

She does this from her fourth-floor office at the Institute of Fundamental Sciences. Dressed in jeans and sneakers, surrounded by books and papers, the diminutive chemist explains that once planning is complete sitting at a computer, she’ll front up in the lab to make the new molecules, step-by-step, tracking changes using spectroscopy of various kinds.

“Instruments like the nuclear magnetic resonance (NMR) spectrometer can give us enough information on an atomic level so we can know, for example, if we’ve replaced a hydrogen atom with an oxygen. “It’s an area of chemistry that’s more art than most. It’s art and science.”

The research group has three major projects under way, all focusing on design, synthesis and evaluation of molecules.

Lead-in work was inspired by a sticky protein excreted by blue mussels. Researchers in the USA had determined the amino acid composition of the molecule, The substance, which sticks the mollusc to rocks remains sticky while under water, lending potential for development as “surgical superglue”, Dr Taylor says.

“We’ve made small versions of the sticky protein but what I have to do now is make it more efficiently and produce a reasonable amount of it so we can do something meaningful with it.

“During the mussel protein work we developed skills in the synthesis of amino acids called hydroxyprolines, and this led us almost inevitably to look at collagens, a family of proteins with all sorts of structural roles – they make up skin, cartilage, nails, hair and bone.”

Collagen can be compared to a piece of rope made up of three strands, intertwined to form a tough fibre. Dr Taylor’s team is looking specifically at the role of hydroxylated prolines and their derivatives, which are found in abundance in the collagens.

“The challenge at a fundamental scientific level is to understand how the amino acid composition translates to the function of the molecules; for example, what makes them very strong or what happens if there is too much carbohydrate?”

The molecules produced in the study, and physical data, will provide a clearer picture of the factors influencing the structure and stability of these proteins, Dr Taylor says.

“And when we start to achieve that, we may even glean insight into the molecular basis of some collagen-related diseases, including arthritis and osteoporosis. If we can understand what’s going on, scientists are then in a position to try and develop therapies.”

Some members of Taylor’s team have recently become part of a subcontracted project with the Fonterra Research Corporation on a Foundation for Research, Science and Technology project worth $570,000 over three years. Initially concentrating on cheese, the team is working on novel flavour compounds that may be used in the food industry.

In 2000, when Taylor moved to Massey University, she received Health Research Council funding of $340,000 over three years to look at the design and synthesis of molecules that might have an impact on diseases, including multiple sclerosis and asthma. This work is in collaboration with the University of Auckland’s Geoffrey Krissansen.

Dr Taylor graduated MSc at the University of Auckland in 1988, having worked with Professor Con Cambie. She used a compound isolated from the native silver pine to produce a molecule of interest to the perfumery industry.

The fascination with organic chemistry grew through two summers (1987 and 1988) investigating the addition reactions of some bright orange compounds with Professor Harold W. Heine of Bucknell University in the US, and continued with a PhD in 1993 from the University of Pennsylvania and a doctoral thesis involving the development of catalytic antibodies for peptide bond formation under Professors Ralph Hirschmann and Amos Smith. During 1993 and 1994 Dr Taylor was a research associate at Princeton University in New Jersey, returning to New Zealand in 1995 to a position at the University of Auckland which involved split teaching responsibilities between the Department of Chemistry and Auckland Medical School.

“That was supposed to be 75:25 but I used to joke it was 90:40,” she says.

Promoted to Associate Professor last year, she combines her research work with teaching.

“Traditionally people talk about an academic position as being 40 percent teaching, 40 percent research and 20 percent admin, but I think the way things are going in New Zealand you are encouraged to excel at it one of these things. You have people who do no teaching … but have other people who do very little research and are committed to teaching. Then there’s those of us who are a bit deluded and try to do everything.”

Dr Taylor’s first academic term this year is immersed in teaching, and she’s considering what “whiz-bang” sideshows she can come up with to capture students who are not chemistry majors. She’s also juggling managing her team, securing research funds, organising international placements and scheduling requests from international bodies who have invited her to speak. Last year she did a six-city lecture tour of British universities, ending in Edinburgh, and this year she’ll speak at the prestigious Gordon Research Conference on Natural Products Chemistry in New Hampshire in July, then later in the year in Philadelphia at a symposium to honour one of her mentors

“I have turned down other opportunities to speak because my teaching schedule doesn’t allow it, and I don’t have an army of 20 people working for me. I need to spend time at home in Palmerston North working in the lab to produce results.

“And I am still teaching because I think students deserve to be taught by research-active people. That’s what a university is supposed to be about.”

Though her research team is small, Dr Taylor prefers it that way. “Because it’s hard to organise people’s contracts, struggle with management and administration. No one teaches you to be a teacher, manager or accountant.

“And I like to keep a pretty close eye on the accounts. We work so hard to get research money and I personally feel a huge amount of accountability to those funding agencies that invest in us – so we try to spend the money wisely.”

The scientific community and university structure at Massey are incredibly supportive, Dr Taylor says, and it is “not impossible” to do really good scientific work in New Zealand.

“But it’s hard to get good people … One of the biggest problems is getting PhD students because there are too many good opportunities for them to go overseas.”

The team is currently composed of two postdoctoral researchers, two PhD students and a visiting student from Germany, with a PhD studentship and research assistant position Dr Taylor is trying to fill. The future looks financially assured thanks to a new Marsden grant of $585,000 over three years confirmed in September 2003. The project is looking at “molecular complexity beyond the genome”, in particular how proteins are modified and manipulated during and after their assembly under genetic control.

"We hear a lot about genomics and we can clone the gene and we can manipulate the gene but where’s the other information? Getting the DNA doesn’t tell us everything. There’s the influence of the environmental conditions, the health of the individual for example.”

A focus of this work is an unusual amino acid called histidinoalanine. This is an example of a protein cross-link, in which two previously distant pieces are joined together in an irreversible manner.

“ The formation of this crosslink is implicated in the ageing process,” Dr Taylor says, “older teeth, for example, have higher levels, and they also occur in cataracts.”

The 37-year-old was presented in 2001 with the prestigious Easterfield Medal, awarded every two years by the New Zealand Institute of Chemistry and the Royal Society (London) to a New Zealand scientist who has made a substantial contribution to chemistry research. Eighteen years into her chemistry career, she’s as enthusiastic as ever.

“Actually making molecules is not a sit on your bum and stare at your computer screen kind of science. It’s get into the lab and find a way to make things work.

“The thrill when you do find something is tremendous. A really good ‘Eureka moment’ only happens every five or six years in my experience, but it’s really, really satisfying. To have an idea and see it through to completion is unbelievably rewarding.”

The process requires “real creativity”, Dr Taylor says with an obvious passion.

“It’s the only game in town; it doesn’t matter how tired you are or how frustrated you are. It’s like a calling. It feels like what you have got to do.”