Research
Research overview: population genetics, evolution and adaptation
Research in the lab is split between two main themes. First, we are interested in the evolution and maintenance of colour polymorphisms, and more generally, how they impact on the speciation and adaptive radiation of snails. This work is mostly being carried out on the charismatic European snail Cepaea and the endemic Japanese genera Euhadra and Mandarina. Second, we have initiated a BBSRC funded programme to establish the pond snail Lymnaea stagnalis as a model for the understanding of the evolution and development of left-right asymmetry. The ultimate aim is to understand how chirality is determined at the molecular level, then extrapolate this to include the means by which variation in sequence, and dominance relations between alleles, contributes to the evolution of new chiral morphs. There are also a number of other projects – research on the conservation genetics of mustelids has been particularly fruitful because it links in to the Conservation Genetics course that I teach. Another avenue is to understand the function of the 'love' dart of snails.
A wide range of techniques are used, including the latest DNA ultra-high throughput sequencing methods, field work, mathematical models, phylogenetics and bioinformatics. Research therefore crosses several other sub-disciplines within the School, including Developmental Biology and Gene Control, and Animal Behaviour and Ecology. We also benefit with strong links to collaborators in Edinburgh (Professor Mark Blaxter) and Japan (Professor Satoshi Chiba). Research is (or has been) largely funded by The Royal Society, the JSPS and the BBSRC.
Downloads of my publications are available from the publications sections of this website. PhD studentships are advertised on http://www.findaphd.com/
Unwinding snail chirality
For an organism to become asymmetric, bilateral symmetry must somehow be broken during development. Although multiple lines of enquiry remain, a deep-seated theoretical problem has stoked a burning interest in understanding the symmetry-breaking event – how is one side of an organism consistently distinguished from the other, given that the side that is called 'right' is essentially arbitrary? In the hypothetical view of Brown and Wolpert, the solution is provided by a pre-existing asymmetric molecular reference: an asymmetric gradient is created if an 'F-molecule' aligns with anterior-posterior and dorsal-ventral axes, so transporting an effector molecule towards the left or right. Asymmetry is thus entirely dependent upon the chirality (and subsequent alignment) of the F-molecule.
To attempt to validate the hypothesis, attention has focussed on the mouse, chick and zebrafish. In these model organisms, it has been found that rotational beating of cilia in the early gastrula creates an asymmetric extracellular fluid movement. It has therefore been argued that this is the symmetry-breaking step – the chirality of cilial motor proteins leads to directional fluid movement, ultimately determining the molecular and morphological asymmetry.
The unfortunate problem, however, is that a body of research indicates that the symmetry-breaking event sometimes occurs much earlier and at the intracellular level, preceding the commencement of ciliary movement. Together, the results suggest that in invertebrates and at least some vertebrates, molecular asymmetry is established early in embryogenesis, with morphological asymmetry only becoming apparent later. In consequence, the field of left-right patterning is "in disarray", because the notion that the rotary movement of cilia determine asymmetry is an elegant hypothesis that is undermined by earlier symmetry breaking events, even in some vertebrates. If the rotational beating of cilia is the symmetry-breaking step in the mouse, then it is probably the exception.
We are therefore developing the pond snail Lymnaea stagnalis as a lab animal to help understand the symmetry-breaking step, following years of neglect. The primary motivation for using Lymnaea is that molluscan asymmetry is established very early, and is genetically tractable; other "genome-era" molluscs do not vary in their chirality and so are of no direct use to this project.
The specific aim of a project that has been funded by the BBSRC is to utilise the power of ultrahigh-throughput DNA sequencing to directly clone the gene for chirality in Lymnaea stagnalis, working on the hypothesis that the maternal determinant of chirality in snail eggs is a molluscan F-molecule, or at least a molecule that interacts with it. With false positives excluded by genetic mapping, we will then attempt to definitively identify the gene with functional and cytological studies.
The general, long-term aim is put in place techniques that will in the future enable a precise understanding of the symmetry-breaking event in snails, stimulating investigative analyses of the same or related molecules in other organisms, including vertebrates. The work is timely because very recent technological advances have made identification of the asymmetry-determining locus feasible within the scale of a three year grant. Much of the work will be outsourced (e.g. sequencing, genotyping).