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). 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.
Research: Technical Summary
We are trying to understand the development of the vertebrate skull and how the relevant embryonic tissues interact with the developing brain at the molecular and cellular level in development and evolution. 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
All our projects harness the power of comparative transgenesis, conditional recombinase-mediated transgenesis and gene ablation, lineage and molecular studies in combination with live imaging in different vertebrate systems, followed by massively parallel single cell tracking and global analyses.
We look at basic molecular mechanisms of cellular communication and lineage choice in the assembly of complex 3 or 4-dimensional structures, in this case teeth, tongue musculature and brain. If you do have a strong neuroanatomical interest in Long Covid and a computational background, there is also a set of projects out there for you.
Beyond some immediate scientific interests I take great interest and care in the education of the researcher of the future, when I am no longer. We have build up structures, ways of how students can interact with each other in new observational platforms to make observations at a scale normally impossible for individual observers. These observations are then the basis for deeper analysis which is exhilarating. If you want to get involved in these projects from a computational and/or experimental side, please drop me a line. We are always keen on extending our team and involving people with diverse and strong interests to solve complex problems at the interface of biomedicine, evolution and developmental genetics.
1988: German High-school (Apostelgymnasium), focus on Classics and Biology
1988-1989 Military service, German Army.
1989-1997: Fellow of German National Scholarship Foundation (Studienstiftung des Deutschen Volkes) for undergraduate and PhD studies.
1989-1994 Studies in Tuebingen and Freiburg: Trained in comparative vertebrate anatomy, genetics, palaeontology, vertebrate embryology and (largely) Greek philosophy. Diplombiologe (equivalent to BSc)
1994-1997:PhD with Professor Andrew Lumsden FRS in vertebrate embryology: Work on the role of neural crest in craniofacial pattern. This work discovered how neural crest segmentation is maintained in the segmentally specific pattern of skeleto-muscular connections, it has taught us for the first time how muscles get anchored onto the right places in the skull and tongue. This work was awarded the Thomas Henry Huxley Prize 1998 for the best zoological PhD thesis in the UK/N.Ireland.
1997-2001: Human Frontiers Long term fellow and BASF special postdoctoral fellow at Harvard University. Also awarded EMBO fellowship (but I declined it). Work with Professor Catherine Dulac (Harvard) and Nobel Prize winner Richard Axel on the development and wiring of the olfactory system (pheromonal perception system): work on genetically tracing neuronal circuitry. First delineating of genetically tracked pheromone circuitry. Learned transgenesis and knock-out technology, ablated Trpc2 which is essential for pheromone perception. This revealed fundamental neuronal mechanisms of how genders are acquired and enacted in the brain. Development of novel methods to expression-profile single cells on microarrays using laser-capture microscopy, a technique still being used in the lab. This pioneering development - to be able to do single cell transcriptomics at specific anatomical (and embryonic) locations - was the seed for a large field which is now called 'spatial transcriptomics'.
April 2001-March 2007: Senior Lecturer in Functional Genomics and Evolutionary biology at UCL (WIBR). Discovery of a novel neural crest origin of the neck and shoulder region (Matsuoka et al. Nature 2005), responsible for the connectivity between head and shoulder girdle. Refocus of work into areas of gene-regulation, cis-regulation within stem cells. 2 Wellcome Trust Programme Grants, 1BBSRC Project grant, 1 ARC grant, several smaller grants.
Since April 2007: Professor of Genomic Systems Biology and Evolution,University of Warwick, School of Life Sciences, Co-director of Warwick Systems Biology (2007-2009) where I taught a whole course on transcriptional regulation, worked on gene regulation and introduced 'matrix management' into student practice.
Awarded Human Frontiers Programme Grant (as Principle Investigator), 2 MRC grants and several Charity grants, hosted several HFSPO postdoctoral fellows. Focus on fundamental aspects of gene regulation and how these relate to anatomical features and how these have been subjected to evolutionary change of craniofacial structures. A most recent MRC project grant with my dear colleague Prof Nick Dale has examined the role of neural crest lineages in postnatal and adult breathing control. Now we are largely studying tongue and teeth and neuroanatomy of Covid infection.