My research investigates the mechanisms of early embryonic development. This is an important topic for two reasons. First, one in six couples have difficulty conceiving a child, a quarter of human conceptions are lost in the first five months, and 2% of children are born with a major genetic defect. Understanding developmental mechanisms can help alleviate these problems. Second, if we understand the mechanisms of normal embryonic development, we can use this information to help direct stem cell differentiation. Much of our work uses the accessible embryos of the frog and the zebrafish, but we also study the mouse as well as mouse and human embryonic stem cells. One of our objectives is to ask to what extent developmental mechanisms are conserved between species.

We study how the central nervous system (CNS) is formed in embryos. Despite its complexity, the CNS is assembled in a remarkably precise and reliable manner. This precision is necessary for the wiring of nerves into the functional neural circuits that gives the CNS its function. Our research focuses on the spinal cord, which is the part of the CNS that contains the nerves that allow us to sense our environment and respond to it by moving muscles. Our goal is to identify the genes involved in spinal cord development and determine how they work to produce and organize the different types of nerve cells found in this part of the CNS. This will contribute to understanding the development of the spinal cord as well as shed light on diseased and damaged nervous systems.

The Worldwide Influenza Centre (WIC) acts as a WHO Collaborating Centre (WHO CC) for Reference and Research on Influenza, one of six in the world. The WHO CC works within the WHO Global Influenza Surveillance and Response System (GISRS). The object of the work is though detailed analysis of influenza viruses from humans (seasonal influenza viruses, zoonotic influenza viruses and pandemic influenza viruses) to assess on a global scale the likely impact of any newly emerging influenza virus for its impact on humans, to address whether there is a need to modify recommendations for vaccines (seasonal and pre-pandemic), to monitor the resistance of viruses in circulation to antiviral medicines and to carry out risk assessments associated with any newly emerging influenza virus. In WIC we collaborate with WHO National Influenza Centres from around the world. We perform antigenic and genetic analysis of viruses and monitor the drug sensitivity of the viruses. WIC also prepares viruses suitable for development for inclusion in influenza vaccines. Currently, because most influenza vaccines are produced in hens’ eggs, these viruses are isolated and propagated exclusively in hens’ eggs. The currently recommended prototype vaccine virus for the H3N2 subtype is a virus from the National Influenza Centre in Hong Kong China SAR and isolated and propagated in WIC (A/Hong Kong/4081/2014).

We aim to both understand and ultimately control the process of cell growth. We are identifying the key proteins that regulate how and when cells divide. We are particularly interested in the arrangement of proteins within cells; just as the placement of gears within an engine is critical for its function, so it is in cells. Many proteins do different things in different places and by repositioning proteins, cells can change their function. We rearrange proteins within cells to determine their function at a specific location and can drag them to new locations within the cell to change the way that they grow. In this way we aim to understand how cells normally regulate their growth and identify ways to modify this.

A long-term challenging problem in biology is to fully understand how a single cell develops into a multi-cellular organism. My laboratory is interested in understanding the molecular mechanisms that control the decision to differentiate from one cell type into another. The budding yeast S. cerevisiae is an ideal model system to study this problem. In response to a combination of extracellular and intracellular cues budding yeast undergoes a highly conserved cell differentiation program called gametogenesis. Since entry into gametogenesis is controlled by only two master regulators in this model organism, there is unique opportunity to study the molecular and quantitative aspects of this cell fate. We are also interested in how gene expression is controlled during the decision and during cell differentiation. Our efforts have in particular focused on how long noncoding RNAs and mRNA isoforms regulate gene expression dynamics during cell fate differentiation. It is our hope that the results from these studies will shed light on how gene expression regulates cell fate in higher eukaryotes including mammalian cells.