Improving our Mechanistic Understanding of Cell Cycle Dynamics

This project falls within the EPSRC "Synthetic Biology" and "Systems Biology" research areas.

The past decades saw enormous advances in biological sciences, resulting in a staggering amount of detailed knowledge about the biochemical reactions and mechanisms in a cell. This knowledge enabled rational design of biological systems, giving rise to synthetic biology as a new engineering discipline. Despite synthetic biology can provide solutions to pressing environmental, medical and ethical problems, intricate interactions of the designed system with its (cellular) environment limit the complexity of synthetic biological systems. An important strategy to overcome this limitation, is to integrate the ever-increasing amount of biological knowledge to a mechanistic, systems level understanding of the processes in a cell.
In this project we focus on the processes that regulate cell cycle progression using the following a four-step strategy. (1) We cast knowledge about biochemical reaction networks into ordinary differential equations (ODEs). (2) We obtain highly multiplexed snapshot measurements of cell cycle regulators in asynchronous cell populations. (3) We computationally reconstruct cell cycle regulator time-courses from our snapshot measurements. (4) We develop optimisation and model reduction/selection toolboxes to fit unknown kinetic parameters of the ordinary differential equations from (1) to predict experimental data from (2, 3).
By building a human cell cycle model as described above, we want to improve our mechanistic understanding of cell cycle dynamics. The cell cycle model shall help synthetic biologists, researchers and medical practitioners alike, for high throughput design and hypotheses testing in silico.

The emerging and dynamic field of Synthetic Biology has the potential to provide solutions to some of the key challenges faced by society, ranging across the healthcare, energy, food and environmental sectors. The UK government has recently a "Synthetic Biology Roadmap", which presents a vision and direction for Synthetic Biology in the UK. The report projects that the global Synthetic Biology market will grow from $1.6bn in 2011 to $10.8bn by 2016. It highlights that there is an urgent need for the UK to develop the interdisciplinary skills required to take advantage of the opportunities provided by Synthetic Biology.

The challenge to the academic and industrial research communities is to develop new translational approaches to ensure that these potential benefits are realised. These new approaches will range across the design and engineering of biologically based parts, devices and systems as well as the re-design of existing, natural biological systems across all scales from molecules to organisms. The techniques will encompass not only individual cells, but also self-assembled biomimetic systems, engineered microbial communities and multicellular organisms, combining multiple perspectives drawn from the engineering, life and physical sciences.

Realising these goals will require a new generation of skilled interdisciplinary scientists, and the training of these scientists is the primary goal of the SBCDT. Our programme will give the breadth of coverage to produce a "skilled, energized and well-funded UK-wide synthetic biology community", who will have "the opportunity to revolutionise major industries in bio-energy and bio-technology in the UK" (David Willetts, Minister for Universities and Science) in their future careers. This will be made possible through genuine inter-institutional collaboration in partnership with key industrial, academic and public facing institutions.

The potential impact of the SBCDT, and its potential national importance, are very therefore high, and the potential benefits to society are significant.