Personal profile

Research interests

Evolutionary Systems Biology

To understand evolution we use a range of tools, from computer models to model organisms, with a focus on experimental evolution. With these tools we ask questions at a range of evolutionary scales, from single mutations to comparisons among species.

 

Mutation rate plasticity

The probability that an organism’s offspring carry spontaneous changes to their DNA sequence depends on many things, including that organism’s environment. We are looking at environmentally dependent changes in mutation rate, or ‘mutation rate plasticity’. We discovered that microbes in dense populations tend to have lower mutation rates than microbes in spread out populations; that is, DAMP: density-associated mutation-rate plasticity. We want to understand DAMP from its mechanisms via how it evolves to the evolutionary effects that it has.

Key current people: Rok Krašovec, Huw Richards, Guillaume Gomez

Key collaborators: Roman Belavkin, Alastair Channon, Andrew McBain, Daniela Delneri

Key papers:

Krašovec R et al. (2014) Mutation rate plasticity in rifampicin resistance depends on Escherichia coli cell–cell interactions. Nat Commun 5: 3742.

Krašovec, R., Richards, H.,et al. (2017) Spontaneous Mutation Rate Is a Plastic Trait Associated with Population Density across Domains of Life. PLOS Biology, 15, e2002731.

 

Antibiotic resistant E. coli

Anti-microbial landscapes

Organisms that are resistant to antibiotics and other anti-microbials are a major and growing issue in medicine and beyond. How this comes about is a question of evolution and we are looking for evolutionary answers. This involves considering the whole ‘landscape’ of organisms’ possible genetic make-ups and their ability to thrive with or without antibiotics. Collaboratively, we are also looking at complete landscapes of anti-microbial peptides and their ability kill particular organisms.

Key current people: Danna Gifford, Christine Joerres, Sam Clark

Key collaborators: Curtis Dobson, Lynda Harris, Roman Belavkin, Alastair Channon

Key paper:

Belavkin RV et al. (2016) Monotonicity of fitness landscapes and mutation rate control. J Math Biol 73: 1491-1524.

 Landscape1

Microbiome evolution

How the diversity of microbes living together in one place changes over time is an example of evolution. Understanding that evolution by following particular organisms, for instance when their environment is changed experimentally, has the potential for insight in systems as diverse as soil and the mammalian gut.

Key current people: Gurdeep Singh

Key collaborators: Franciska de Vries, Sheena Cruickshank, Andy Brass, Kelly Ramirez

Key paper:

Ramirez KS, Knight CG et al. (2017) Detecting macroecological patterns in bacterial communities across independent studies of global soils. in revision.

microbiome tree

Genotype-phenotype map in evolution

How do the individual DNA changes used by evolution (genotype) affect the behaviour of the complex system that is the living cell (phenotype)? How do organisms manage to evolve at all when even a small genetic change may affect many different aspects of the cellular system? How do the changes to genotype and phenotype used by short-term evolution relate to the changes seen across longer-term evolution, within or among species? We want to answer such questions using a combination of wet-lab and computational approaches.

Key current people: Robert Hohan, Chengyang Ji

Key collaborators: Russell Garwood, Rob Sansom

Key papers:

Knight CG et al. (2009) Array-based evolution of DNA aptamers allows modelling of an explicit sequence-fitness landscape. Nucleic Acids Res 37: e6.

Knight CG et al. (2006) Unraveling adaptive evolution: how a single point mutation affects the protein coregulation network. Nat Genet 38: 1015-1022.

Network1

 

Other important people, including collaborators and PhD students (current and former)

Mariana de la Pena, Sam Farrell, Douglas Kell, Armand Leroi, James McInerney, Ignacio Medina, Gino Poulin, Paul Rainey, Dan Smith, Adriana Vintilla, Feng Xue.

 

If you’re interested in joining us, see the Opportunities tab

Biography

2017 – present

University of Manchester, Faculty of Science and Engineering, Senior Lecturer

2012 – 2017
University of Manchester, Faculty of Life Sciences, Lecturer

2008 – 2013 University of Manchester, Faculty of Life Sciences, Wellcome Trust Research Career Development Fellow

2005 – 2007
University of Manchester, Manchester Interdisciplinary Biocentre, BBSRC Postdoc with Douglas Kell

2002 – 2005
University of Oxford, department of Plant Sciences, NERC Postdoc on the molecular basis of evolution in the bacterium Pseudomonas fluorescens with Paul Rainey and the proteomics lab in the department of Biochemistry.

1997 – 2001
Imperial College London at Silwood Park, PhD on ‘The genetics and evolution of body size in the nematode Caenorhabditis elegans’ funded by NERC, supervised by Armand Leroi

1994 – 1996
Christ's College Cambridge, MA Natural Sciences, finalising in genetics

Overview

Experimenting with Evolution

We want to understand the mechanics of evolution. Exactly what molecules change? In what ways are these changes beneficial (or not) to the organism? How does this relate to what happens in populations of organisms? We mostly answer these questions using microbes. This means that our work relates to issues from the rise of antimicrobial resistance (AMR) to the roles of microbiomes – the mixed populations of microbes in particular places, from soil to our guts. Microbes reproduce fast enough that we can watch evolution happening in real time on the lab bench. To make sense of what’s going on we use computational models. Our mixture of wet-lab and computational approaches means that we collaborate both with other biologists, contributing quantitative approaches, as well as computer scientists and theoreticians.

Opportunities

We are always looking for people interested in joining the lab. In the first instance, please send me an email and CV outlining your interests and experience.

PhD opportunities

Current opportunities I’m involved with, advertised at findaPhD.com, should be listed below. These are mostly via the University of Manchester’s BBSRC, MRC and NERC doctoral training partnerships. If you have access to other sources of funding, get in touch and/or consider the available project outlined below.

Fellowship and postdoc opportunities

If you're interested in applying for a fellowship to work with us, there is a range of possible funding sources, both external (e.g. Wellcome Trust, Royal Society, BBSRC, NERC, HFSP and EU) and internal (e.g. look out for repeats of this).

PhD project: Mutations in space

Spontaneous mutation supplies the raw material for evolution, but we find that the rate at which it occurs can vary with the environment in non-obvious ways. Most of what we know about variation in mutation rates comes from microbes growing in shaken liquid cultures. These environments have little spatial structure. However, in many, ‘real’ environments, from soil to skin, spatial structure really matters. Using a range of techniques for estimating and modifying mutation rates in model microbes, the student will determine how space matters for that fundamental first step of evolution – does mutation rate change with the degree of spatial structure? Does the association of mutation rate with population density hold for spatially structured environments? What genes are required? Training will be provided in necessary skills, but the student would ideally have a background in biology or genetics with computational skills and a keen interest in evolution.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 13 - Climate Action
  • SDG 15 - Life on Land

External positions

Pool of Experts, Biotechnology & Biological Sciences Research Council (BBSRC)

1 Jan 201731 Dec 2022

Research Beacons, Institutes and Platforms

  • Digital Futures
  • Institute for Data Science and AI
  • Manchester Environmental Research Institute

Keywords

  • Experimental Evolution
  • Microbiology
  • Modelling
  • Pleiotropy
  • Epistasis
  • DNA damage
  • DNA repair
  • Synthetic biology
  • Simulation
  • Experimental Design
  • Statistics
  • Genotype-by-environment interaction
  • Environmental change
  • Survival of the flattest
  • Critical mutation rate
  • Fluctuation test
  • Networks

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