Professor Maggie Smith

Associate Head of Department

Overview

Molecular Genetics of the antibiotic-producing bacteria Streptomyces and their bacteriophages. 

 

Bacteria in the genus Streptomyces are prolific producers of antibiotics, anti-cancer agents, immune-suppressants, and other bioactive natural products. The aim of Maggie Smith’s research is to investigate and exploit genetic processes in Streptomyces and their close relatives to facilitate novel drug development.


Colonies of Streptomycelividans growing on an agar plate. The fuzzy surface of the colonies indicate the formation of spores.

colonies of S. lividans

A major theme in Maggie’s lab is to study the genetics of host-phage interactions. A new family of phage-encoded integrases, the serine integrases were first characterised in Maggie’s group. Integrases are natures DNA cut and paste tool and can be used to integrate and excise DNA from chromosomes. This is a useful tool for genetic engineering and has been deployed in bacteria, fungi, animals and plants.  In Streptomyces sp. vectors based on serine integrases are widely used to transfer genes for antibiotic biosynthesis between strains. Maggie’s lab have studied many different serine integrases and are now using them to create stable vectors for the cloning and design of new antibiotics analogues based on erythromycin.


Streptomyces grows with a mycelial growth habit that can be seen under the microscope. 

S. coelicolor hyphae

Left: An electron micrograph of a Streptomyces phage, Joe. Joe was isolated from soil and uses Streptomyces lividans as its host.  

Right: Phage infecting a lawn of Streptomyces growing on an agar plate. Each dark zone or plaque is derived from a single phage particle which kills the bacteria. 

EM of Joe and phage plaques

In other work mutants of Streptomyces were isolated that are resistant to some phages and, surprisingly, hypersensitive to certain antibiotics including two of the last resort antibiotics the carbapenems and vancomycin. These mutants are defective in protein glycosylation. This discovery is being studied further to try to understand the underlying processes that lead to antibiotic hypersensitivity. The goal is to translate this research to pathogenic bacteria to see if we can identify new targets for co-drugs that can be used in conjunction with existing antibiotics to make them more effective.


Strains of Streptomyces coelicolor that are defective in modifying membrane proteins with sugars are hypersensitive to some antibiotics. The plate on the right is sensitive to vancomycin whereas the normal strain on the left is resistant.

Vancomycin sensitivity assay

Research Group

NameStatusProject
Dr Nicholas Read Senior Technical Researcher Overcoming antibiotic resistance by studying antibiotic hypersensitivity

Ms Tessa Keenan

PhD Student Overcoming antibiotic resistance by studying antibiotic hypersensitivity

Mr Nathaniel Holman

PhD Student Overcoming antibiotic resistance by studying antibiotic hypersensitivity

Dr Hong Gao

Postdoctoral Research Associate  A platform for rapid and precise DNA module rearrangements in Synthetic Biology

Ms Gabrielle Taylor

Technical Researcher A platform for rapid and precise DNA module rearrangements in Synthetic Biology

Dr Steph Evans

Post-Doctoral Research Associate  Developing platforms for the production of diterpenoids

Dr Janina Hossbach

Post-Doctoral Research Associate   A platform for rapid and precise DNA module rearrangements in Synthetic Biology

Teaching and Scholarship

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‌My goal as a teacher is to instill understanding, underpinned by knowledge. I believe that students should be equipped with sufficient knowledge to understand principles, which can be used to extrapolate and develop ideas. I want students to question evidence and develop their critical thinking. I like to see students having ideas that others have had previously, as this is the way to original and creative thinking.

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‌As a molecular microbiologist, my lecture material is the amazing world of microbes. My teaching is inspired by my research topics, which are centred on the soil bacteria, Streptomyces. These remarkable bacteria are the most prolific producers of secondary metabolites, which include antibiotics, anticancer agents, immune-suppressants and other bioactive agents used in the pharmaceutical industry. How are these metabolites made? What tools do we need to make/discover new antibiotics that are urgently needed?

The genetic engineer uses tools to cut and paste DNA and in our lab we are using phage encoded recombinases, to do just this with antibiotic pathways. However a good worker knows how his/her tools work, so I am interested in how some of these recombinases work. Some of these proteins are beautiful molecular machines. It is my aim to try to convey state of the art knowledge and understanding in both DNA recombinases and Streptomyces genetics and biochemistry.

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I touch on a broad range of topics in tutorials, but still in the fields of molecular biology and microbiology.  Tutorials are a forum for students to learn and practice how to question, have ideas and to discuss topical scientific issues.  Quite often the subject of the next tutorial is inspired by something in the press. I have no prescribed pattern of topics for each tutorial. Students are sometimes given a free hand at picking a topic for the tutorial, encouraged to go out and follow their interests. 

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Students taking a project in my lab will inevitably be working on something aligned with our research. The isolation of new bacteriophages is usually an option as at the heart of my research is the interaction between phages and their bacterial hosts. Almost all of our research projects have come from asking questions about phage-host interactions.  The sort of techniques the student will learn include microbiology, some DNA manipulation and some bioinformatics. 

Publications


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Maggie Smith 218

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Contact details

Prof. Maggie Smith
Department of Biology
University of York
Wentworth Way
YO10 5DD

Tel: +44 1904 328686