Dr Louise Johnson, a population geneticist working on the evolution of genetic systems, has been an Associate Editor for Methods in Ecology and Evolution since October 2013. In that time she has handled a range of manuscripts falling within her areas of expertise (primarily molecular evolution, population genetics and genomes).
Louise began her academic career with a degree in Genetics at the University of Edinburgh. She then moved south to complete her PhD on the evolution of mating systems in yeast at Imperial College London under the supervision of Professor Austin Burt. Following her successful time in London, she took up post-doctorate positions at the University of Nottingham (working on transposable elements with Professor John Brookfield) and across the Atlantic at the University of Virginia (looking at genome defences with Professor Janis Antonovics and Professor Michael Hood). Louise returned to the UK in 2006 to take up an RCUK Fellowship at the University of Reading and has been there ever since.
As part of our series of Editor Profiles, we asked Louise to tell us about some of her current research:
There are three projects which I am currently working on that I would like to outline. I’ll be discussing the cancer project – or at least the story so far – at the Methods in Ecology and Evolution 5th Anniversary Symposium later this month. Do check out the programme, and I hope to see you there! The whole point of a methods journal is to help each other do our research as well and easily as possible, so there’s a built-in community spirit about MEE, which bodes well for a fun and useful meeting. Before I start I should also say that I’m lucky to have amazing collaborators at Reading and beyond: for the projects below, credit is particularly due to my colleagues Rob Jackson and Tiffany Taylor, who had a huge input, and to Mike Brockhurst at York.
Evolution of Genetic Codes
I have a long-standing interest in the evolution of the genetic code (and don’t get me started on the way the media use “genetic code” interchangeably with “genome sequence”). The code is right at the heart of how life works, and it does its job very well – for example, it minimises the effect of mutations – but at first sight it appears that the code should be almost un-evolvable, due to strong constraints on its function. Recent evidence from environmental genomics and metagenomics suggests that genetic codes may be more variable and flexible than we thought though. I’ve done theoretical and bioinformatic work on how and why the code might evolve adaptively and over the past few years I’ve added an experimental approach. We’re currently analysing the data from a Leverhulme-funded project where we tweaked the genetic code of E. coli and evolved them for many generations to allow the genome to coadapt, to monitor the recovery of fitness and detect the genomic changes responsible.
This research spun off from an applied microbiology project on plant growth promoting bacteria by Abdullah Alsohim, at the time a PhD student in Rob Jackson’s lab. He had genetically engineered some completely immotile strains of bacteria by deleting the “master switch” gene for flagella production and then disrupting a second, surfactant-based motility system. To his initial confusion, given 48-96 hours’ incubation, these strains would consistently regain flagella and the ability to swim. Using whole genome resequencing and gene expression analysis, we were able to work out how this had happened: flagella were regained in a two-step process that involved replacing the missing switch by co-opting a related nutritional regulator. The cost of this co-option was that the bacteria with re-evolved flagella lost their ability to regulate nitrogen intake. We published this result last month and we’re now working on other ways to use this as a test case to understand how natural selection can rewire gene regulatory networks. In particular, we’re currently repeating the evolutionary process on different nitrogen sources to influence whether the mutations involved are beneficial or deleterious, so we can see if the regulatory network evolves differently depending on the shape of the adaptive landscape.
Cancer is now well understood to be an evolutionary process – a failure of multicellularity in which the cancerous cell lineage cheats its fellows. Most cancer evolution research is observational rather than empirical. However, microbiologists have developed hugely successful protocols for testing causal hypotheses via experimental evolution: they simply apply selection in the lab and follow the evolutionary process in real time with appropriate replication and controls. With Phil Dash, a cancer biologist at Reading, we have been using cancer cells grown in vitro for experimental evolution, as we suggested in this Perspectives paper. Obviously, human cancer cell lines are very different from bacteria: they’re slow-growing, fussy, and to confuse matters further they have complex, epigenetically-controlled responses to their environments.So our valiant PhD student, Ana, has been doing a lot of work in adapting techniques to suit the system – keeping in mind a favourite quotation from Thomas Edison: “identifying 10,000 ways that don’t work is not failure”.
If you’d like to see Louise’s talk on cancer cell evolution at our 5th Anniversary Symposium, you can register up until Friday 10 April. For registration and more information on the event, click here.
Follow Louise on Twitter: @louisejjohnson