What gives a cell its identity? Lizzie uses her diverse experience in psychology, neuroscience and systems biology to answer this question, and to define how the lymphatic system develops
I have never had burning aspirations to be a scientist. In high school my best subjects were English and languages rather than STEM, but I enjoyed biology the most. As a 15-year-old my parents told me that if you do what you love work won’t feel like “work”, and I have made all my career decisions based on this advice. As a result, I have a broad range of cross-disciplinary experience, and my career trajectory differs considerably from that of my peers. I hold a BSc in psychology and neuroscience with honours in developmental biology, and a PhD in systems biology of stem cells and human development. Over the last decade I have conducted wet-lab research in Australia and the USA in entomology, molecular neuroscience, quantitative genetics, human stem and iPS cells, and dry-lab research in developmental biology using bioinformatics and systems biology. Since 2019 I have been working with Professor Ben Hogan, using computational and systems biology to understand how the lymphatic system develops. The common theme throughout my research is the motivation to describe and predict what gives a cell its identity, and what pushes it to change identity during development.
Understanding what defines a cell and how cells choose a particular fate from a variety of options during development is challenging, but I hope to answer these questions by drawing inspiration from the work of developmental biologist Conrad Waddington. His famous Epigenetic Landscape and the lesser known concept of canalization are useful metaphors that help us understand these developmental decisions. As cells move down a landscape during development, they undergo stepwise restrictions in their developmental potential, completing their journey when their identity is mature and not easily changed. Development proceeds along a most favoured or “canalized” path, such that cells exhibit regulative behaviour when their journey is disrupted by environmental change or perturbation, to return to the normal path. During normal development these cell-fate transitions are predictable and usually but not always irreversible, continuously steered by specific groups of signals interacting in the context of a network. The shape of the landscape (topology) is determined by the behaviour of our genes that work together in a network, such that every point in the landscape provides the molecular snapshot of a corresponding cell state. The precise position an individual cell occupies in this landscape encodes a degree of variability, such that a cell can make minor changes to its journey without changing function. I use these concepts as a model to understand how blood cells decide to take on lymphatic identity, and the level of constraint required to maintain this choice.
My research in the Hogan Lab focuses on understanding the transition from blood cell to lymphatic cell fate during development, we use as a model organism the zebrafish. Lymphatic vasculature development is an important feature of wound healing and repair but is also involved in cancer metastasis, so there is a real clinical need to describe, predict and control lymphangiogenesis. I work with genomic data at the population and single cell level that captures the early cell fate decisions in the development of the lymphatic system, and use systems biology to define the network of genes specifying lymphatic identity. I am currently building a landscape of lymphatic development that encompasses this gene network and the range of profiles it confers, enabling me to map most common developmental path. This provides insight into how all genes in the network cooperate to produce lymphatic identity and plasticity, enhancing our ability to describe, predict and manipulate cell behaviour in a wide range of therapeutic contexts.
Adaptation of Conrad Waddington’s Epigenetic Landscape of Development. (A) The path followed by a cell (ball) as it traverses the landscape corresponds to its developmental history. The blue path represents the most common path of development, each point represents a cell identity, and the depth represents how stable it is. (B) The network underlying the landscape controls its shape. The boxes are genes in the network that give a cell its identity and the lines describe how they are related.
Working at the Peter Mac with the Hogan Lab team has enabled me to continue my developmental research question in the context of cancer, where the impact of our research can translate to a real clinical outcome, something I have never considered possible. It is for this reason that I consider myself to be so privileged, I wake up every day to do a job that inspires and excites me, and could potentially improve lives of many people around the world. I could not think of another career that would make me happier, which is all my parents ever wanted. Work certainly does not feel like “work”, it is so much more than that.
Dr Lizzie Mason is a postdoctoral researcher in the Hogan Lab at Peter Mac Callum Cancer Centre and the University of Melbourne. She is an expert in systems biology of development, wet and dry lab transcriptomics and gene expression variability. She was the recipient of the Donald Tugby Prize for Nanotechnology and the Future of Science in 2015, from the University of Queensland.
Lizzie can be contacted via:
Email at [email protected]