The generation and evolution of biological form

Large organisms, like animals and plants, are made from enormous numbers of cells that work together. Under the microscope, one is struck by the extraordinary beauty and complexity of each individual “eukaryotic” cell in the collective. My team is fascinated by ability of these cells to rapidly reshape themselves to give rise to new structures, especially during division, as one cell becomes two.
We are also interested in the origins of complex cells. Remarkably, eukaryotes first arose over 1 billion years ago as the result of a merger between a relatively simple archaeal cell and a bacterial cell. While it is not known precisely how this happened, we recently proposed that eukaryotic cell architecture evolved in a step-wise manner, from the ‘inside-out”, as an archaeal host cell elaborated protrusions that it used to share resources with its free-living bacterial partner. If true, features once thought to be unique to eukaryotic cells may have their origins in archaea. This is a hypothesis we now aim to test.
Finally, by studying cell division in archaea and eukaryotes, we also expect this work to reveal new fundamental aspects of the cell division process that can be used to aid our understanding of human cancer.

My lab is interested in the generation of biological form or “morphogenesis”. Our focus is on events at the cellular scale, because the cell is the unit of life and because even large-scale tissue movements are driven by changes in the shape and mechanical properties of individual cells.
The most extraordinary and fundamental of all morphogenetic events is cell division: the process by which one cell becomes two. During division, in the space of a few minutes, all the component parts of the cell must be moved apart and partitioned into two daughter cells. This must be done with precision, since errors are associated with diseases like cancer in humans, and frequently cause cell death.
Rapid changes in cell organisation, including those that accompany cell division, are brought about by a network of dynamic polymers - the cytoskeleton - which convert chemical energy into force. Strikingly, recent phylogenetic studies have has shown that the key cytoskeletal elements used to drive division and other shape changes in eukaryotic cells (actin, tubulin and ESCRT-III) are ancient proteins, which eukaryotes likely inherited from their archaeal ancestors. Taking advantage of this discovery, in exploring the fundamentals of the division process my lab is looking for similarities and differences in the mechanisms archaea and eukaryotic cells use to divide. Using eukaryotes and archaea (with a focus on Sulfolobus) as model systems, we aim to identify conserved processes, core principles, and to determine how division has changed during the transition from archaea to eukaryotes. We also expect this work to shed light on the process by which the eukaryotic cell first emerged from the symbiosis of an archaeal cell and its bacterial partner – something that remains one of the greatest mysteries in the history of life on earth.
Given the fundamental nature of cell division, we also expect this work to improve our understanding of the way the core division machinery functions to aid normal tissue development and homeostasis and, when it goes awry, contributes to the evolution of metastatic cancer.