Embryonic development orchestrates the proliferation and differentiation of many hundreds of cell types that will interact to form tissues, underpinning organ and organismal function. It is essential to understand the normal processes that regulate the remarkable achievement of embryogenesis in order to have the knowledge necessary to harness the potential of stem cells and gene editing to develop new therapeutics to benefit society. We use non-mammalian vertebrate embryos to study developmental mechanisms. The models used in our labs are Xenopus laevis and tropicalis and the zebra fish, Danio rerio.
Differential gene expression drives the establishment of distinct cell lineages during development and the regulation of protein coding genes has been widely studied. For instance, the establishment of the myogenic cell lineage requires a set of bHLH transcription factors known collectively as myogenic regulatory factors (MRFs) that include myoD, myf5, myogenin, and MRF4 (reviewed in Pownall et al, 2002). These factors are central to a gene regulatory network (GRN) that promotes proliferation of a progenitor population with myogenic potential and later activates the coordinated transcription of genes that code for contractile protein. My lab has defined a role for FGF signalling in the early activation of MyoD in gastrula stages of Xenopus development (Fisher et al, 2002; Burks et al 2009) and we have used transcriptomics to identify the targets of MyoD at this early stage of muscle specification (Maguire et al, 2012, McQueen and Pownall , 2017) continuing our investigation into the signals and transcriptional hierarchies that regulate skeletal muscle development.
Heparan sulfate proteoglycans (HSPGs) are important regulators of FGF signalling and can be structurally modified by the extracellular 6-O-endosulfatase, Sulf1. My lab has helped to demonstrate that Sulf1 is a potent negative regulator of FGF signalling (Wang et al., 2004; Freeman et al., 2008) and that Sulf1 also impacts other signalling pathways that require HSPGs, such as Shh, BMP and Wnt (Ramsbottom et al, 2014, Meyers et al, 2013, and Fellgett et al, 2015) where it acts to influence diffusion of ligands and shape gradients. A BBSRC funded collaboration with Prof Stefan Hoppler (Aberdeen) and Prof Masanori Taira (Tokyo) interrogates how feedback of Wnt signalling can modify ligand diffusion.
It is a privilege to interact with young people and to be given the opportunity to influence their thinking and their understanding of Biology and the scientific process. My enthusiasm for research in the area of molecular embryology is the foundation for my teaching and I try to convey the importance of critical thinking and problem solving by introducing key methods used for understanding embryonic development early in the curriculum.
I teach in all stages of the undergraduate courses we offer in Biology, Biochemistry, and Biomedical science degrees. In the first year module ‘Cell and Developmental Biology’, I introduce the importance of cell signalling and transcription factors in regulating early developmental processes. In the second year module ‘Developmental Biology’, we delve into gene hierarchies and morphogens that pattern early embryos providing a good foundation to students in cell and molecular mechanisms that underpin development. This groundwork allows us to offer a journal club style stage 3 module focussed around selected papers from the primary literature: while challenging the students, this module provides an opportunity for them to gain good understanding of molecular methods used to investigate developmental mechanisms and more broadly how scientific research works.
Small group teaching in my office gives students the freedom to ask questions and discuss science in a friendly, supportive environment. My tutorials take the form of student led presentations and discussions based around pre-set topics on the molecular basis of development and human diseases.
Research projects for undergraduates taking BSc or Integrated Masters degrees in Biology, Biochemistry, and Biomedical science are available in my lab. These projects are related to ongoing research in my lab using frog and fish embryos to understand genes that regulate vertebrate development.