All our projects harness the power of comparative transgenesis, conditional transgenesis and gene ablation, lineage and molecular studies in combination with live imaging in different vertebrate systems.
We are interested in deciphering the complex signalling relationships during craniofacial development by combining the power of developmental genetics, lineage analysis and in vivo single cell imaging across vertebrate systems. One key organizing tissue, the embryonic neural crest, has been the focus of my attention for the past 2 decades. Understanding how it interacts and builds complex patterns of bones and tongue muscles and what it influences (i.e. the brain) and how this has changed over hundreds of millions of years is a great challenge. Deciphering this has relevance for the deep evolution of the vertebrate skeleton & the skeleto-muscular systems. We work on teeth as we have discovered entirely new episodes of cell migration and lineages involved that have so far been missed. And we work on the development of the tongue as it is the most complex structure (involving 9+ muscles and many more different muscular subsystems within each muscle) after the brain and its muscular pattern is the result of complex neural crest cell migration patterns that are happening in a very narrow but critical time window that we are exploring. In recent years we have also started to look into the pathways through which viruses (such as SarsCov2) can travel through the brain but we are unable to experiment ourselves on this virus: we have partners who do that abroad and who share their data with us. I also have collaborations with some key palaeontologists on the histogenetic evolution of skeletal craniofacial structures.
Our main conceptual interest is to track lineages across organisms, look at its evolution through ontogenetic and deep time in order to understand both their evolutionary history responsible for the diversity of craniofacial, tongue, tooth shapes as well as their biomedical relevance in order to understand complex human diseases (Down Syndrome). . We enjoy tracing cell lineages and other biological phenomena across scales of organization from gene-regulation to macroevolutionary anatomical novelties Nature vol 451 No 7179 pp 658-663 Feb 2008 10/1038/451658a paper.
Early embryonic lineages become cryptic, are not visible easily by eye but require fancy genetics and fancy microscopes to be revealed. Currently we work on the early formation of teeth and the way how muscular patterns for within the mammalian tongue - which is relevant for both evolution of muscular systems and the understanding (and hopefully future care for people with) Down Syndrome. All this involves imaging, massively parallel single cell tracking and behavioural analysis of cells navigating through complex tissues.Massively parallel cell tracking involves building communities of observers that all contribute to data flows into an analytical pipeline: a way of crowd-sourcing data by engaging and training many (student) observers. The way we build such communities is rather technical but is inspired by principles taken from Chinese philosophy and US Marine Corps Special forces training principles. In future, this will be linked to spatial transcriptomics, a passion of mine whose core technologies I had pioneered 20yrs ago (then combining laser-capture mediated single cell isolation followed by microarray single cell transcriptome analysis). New tools have emerged in spatial transcriptomics and we will exploring how we can interface our current live imaging capabilities with single-cell spatially resolved transcriptomics (and spatial proteomics). This will enable us to find the molecular causes for the different behaviours we see through our imaging platforms and provide the causative underpinnings of the new migratory paths and pathways that we are currently discovering. All this requires the collaboration of biologists, engineers, analysts, bioinformaticians and other specialists. So if you have a computational background and/or are passionate about unravelling complexity in vertebrate development, evolution or neuroanatomy, please feel free to contact me to explore if there is a path of engagement.
If you are enthusiastic about solving complex puzzles across molecular and systemic levels - and beyond the boundaries of single disciplines, please feel free to contact me anytime.
Kate Jordan, my fantastic graduate student, was awarded the Thomas Henry Huxley Prize and Marsh Medal for the best zoological PhD thesis in the UK and Northern Ireland. Well deserved, Kate, you discovered an entirely novel mechanism of cranial bone formation and worked very hard for this. This will shed new light on bone evolution, development, cancers and will help bioengineering bones. It was a tremendous privilege working with you!