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He is an assistant professor in chemistry, biochemistry and computer science at the University of Colorado at Boulder, and the award is from the Howard Hughes Medical Institute.
Prof Knight (32) was born in Dunedin, attending College St School and Otago Boys High School, later gaining a BSc from Otago University before gaining a PhD scholarship to Princeton University, in the United States.
In 2001, his thesis on the Origin and Evolution of the Genetic Code won an award from the US Council of Graduate Schools for best PhD thesis in life sciences.
Otago University biochemist Prof Warren Tate said Prof Knight had been "a special kind of student" at the university, and had now been further recognised as a leading researcher who was playing a trail-blazing role in his field.
Prof Knight credited much of his success to his training at Otago University and praised Prof Tate's "brilliant lectures" on RNA, which had first roused his interest in this area.
More than 2000 people put their names forward when the institute announced its new Early Career Scientist programme last year, inviting applications from the best early career scientists in all areas of basic biological and biomedical research.
The 50 scientists selected for the award will have their full salary provided by the institute for six years.
Each researcher also receives a research budget of US$1.5 million and other expenses, including research space and the purchase of critical equipment.
Prof Knight and his research group combine computational and experimental techniques to investigate the evolution of the composition of biomolecules, genomes and the human microbiome.
The human microbiome referred to the genes of the 100 trillion or so microbial cells that live in and on our bodies, outnumbering cells with the human genome by as many as 10 to one and "contributing many metabolic functions such as energy harvest and vitamin synthesis that we would otherwise lack", Prof Knight said in an interview.
"Most of these microbes are harmless or beneficial, and understanding their roles in health and disease is crucial," he said.
"In the past two years we have developed a new technique called barcoded pyrosequencing, which allows us to collect information about hundreds of microbial communities simultaneously and gain a much broader view of microbial diversity.
"The award will allow me to unite the narrow views of microbial diversity we get from our other projects on obesity, inflammatory bowel disease, malnutrition, and soil biogeochemistry into a broader vision of how microbes interact in a range of environments, including our own bodies," he said.