Continuing our series of articles on Great British bioscience pioneers, Sir David Hopwood FRS, Emeritus Fellow at the John Innes Centre recounts his career at the forefront of research on the antibiotic-producing bacterium Streptomyces.
How did your bioscience career first begin?
"After graduating in botany from the University of Cambridge in 1954, I sought a PhD topic in the up-and-coming field of microbial genetics. It was suggested that I work on a member of the group of soil-inhabiting microorganisms called the actinomycetes, which were beginning to be important as producers of medically important antibiotics but which were a 'Cinderella' group from a genetic standpoint. Thus began my career-long interest in this group of microbes."
What are you working on now?
"I have been emeritus since my formal retirement in 1998 but I maintain a keen interest in advances in techniques for the discovery of novel antibiotics and other useful specialised metabolites via genetic approaches. A key finding from the complete genome sequence of Streptomyces coelicolor – later shown to be a general feature of antibiotic producing microorganisms – was that the genome contains far more clusters of genes for the biosynthesis of specialised metabolites than are revealed by traditional screening approaches.
"The current challenge is to discover efficient methods to 'wake up' these 'sleeping' genes to gain access to a gamut of novel compounds to evaluate as leads in the quest for antibiotics to fight the threat of increasing resistance to current antibiotics."
What advances have you seen in your chosen field in the last 20 years?
"Our understanding of the genetic control of antibiotic biosynthesis has been revolutionised over the last two decades. Sequencing of the gene clusters responsible has greatly facilitated prediction of the biosynthetic pathways as well as allowing the rational construction of microbial strains able to produce novel compounds or to make known compounds more effectively. This bringing together of molecular genetics and natural product chemistry has been one of the most gratifying outcomes of research in my field.
What are the five key bioscience milestones that you've been part of and when did these occur?
- 1957: Discovered genetic recombination by a novel form of conjugation in the actinomycete Streptomyces coelicolor.
- 1960: In collaboration with Audrey Glauert of the Strangeways Laboratory in Cambridge, discovered that Streptomyces species and, by implication, other actinomycetes are bacteria. They had commonly been thought to be intermediate between bacteria and fungi or even fungi. This finding had a major bearing on the subsequent development of methods for their genetic understanding and manipulation.
- 1985: In collaboration with groups in Japan and the USA, generated the world's first hybrid antibiotic by genetic engineering between different streptomycetes.
- 1993: In collaboration with my former post-doc, Chaitan Khosla, by then a professor at Stanford University, developed rational genetic engineering methods to produce 'unnatural natural products' by combining components of polyketide synthases from different streptomycetes.
- 2001: Co-ordinated the sequencing, at the Sanger Institute, of the genome of Streptomyces coelicolor – the largest microbial genome to be sequenced at the time.
How has BBSRC supported you throughout your career?
"I moved from the University of Glasgow to the John Innes Institute (now Centre) in 1968 as head of the Genetics Department and so the research of my group benefitted from support from the grant-in-aid to the Institute from the Agricultural Research Council, later the Agricultural and Food Research Council, and finally BBSRC until my formal retirement in 1998. This, supplemented by graduate studentships, small industrial grants and EU funding, provided the continuity of support to carry out a systematic study of Streptomyces genetics over a long period of time, acting as a focus for the development of an international community of researchers to drive the field forward."