Nature's medicines

Professor Margaret Brimble is a modern-day alchemist, turning natural products such as shellfish toxins and compounds isolated from rare fungi into new drugs to fight cancer, Alzheimer's and heart disease.

Third-year PhD student Tsz Ying Yuen, Margaret Brimble, second-year PhD student Orla Finch.

The natural products in Margaret’s research are based on are produced by microorganisms that inhabit extreme environments, including an abandoned copper mine in Montana where the pit has filled up with a soup of acidic, metal-laden water. “This is an incredible source of fungi that produce anti-cancer compounds,” she says. “From these we are making compounds based on a unique natural product called berkelic acid, which works on enzymes involved in the spread of cancer.”

Margaret and her team at The University of Auckland’s Medicinal Chemistry Laboratory study and construct the cancer-fighting molecules synthetically. “Nature throws up complicated chemical structures that have evolved over thousands of years for a specific purpose. If we can fine-tune their molecular structure we can create potential drugs even better than nature can provide.”

The laboratory is also studying the potential of natural products produced by marine algae during coastal algal blooms. “The algae produce natural toxins as a defence mechanism against predators but these toxins also activate specific receptors in the human brain,” explains Margaret. “This has implications for people suffering from schizophrenia and Alzheimer’s so we’re synthesising the toxins in the laboratory. We then model the active features of the molecule and try different versions, in different positions, until we come up with the ideal drug.”

About 60% of all new drugs approved by the US Food and Drug Administration are inspired by or made from natural products. Margaret compares creating a synthetic compound from nature to composing a piece of music or creating a beautiful artwork, “it demands academic and manipulative rigour, creativity, dedication, persistence and hard work.”

A trailblazer for women in science, Margaret was the first New Zealander to become a L’Oreal-UNESCO Women in Science laureate in 2007, and remains the only one. She has now been recognised internationally as one of the top in her field by winning the UK Royal Society of Chemistry’s 2010 Natural Product Chemistry Award.

More than 20 PhD students work in Margaret’s laboratory, collaborating with researchers in Hong Kong and China to come up with new drugs for neurodegenerative diseases.

Through a contractual agreement with Auckland Uniservices Limited, the lab has already delivered a commercial drug candidate called NNZ2566 for the New Zealand biotechnology company Neuren Pharmaceuticals. NNZ2566 protects brain cells from dying after a traumatic head injury. With $18 million in funding from the US army, the drug is now in phase 2b human clinical trials and is being tested in trauma centres around the world.

“If it goes to the market it will be the first drug for traumatic brain injury,” says Margaret. “It will put The University of Auckland and New Zealand on the international map as a world class hub for drug discovery and development.”

Read the profile for Professor Margaret Brimble.

This article first appeared in AucklandNow (Issue 5, October 2010).

Professor Brimble was appointed  a Companion of the New Zealand Order of Merit (CNZM) for services to science in the New Years Honours List 2012.