Programmed assembly of protocellular materials

Life is an expression of molecular chemistry. We know that living cells and tissues are an assembly of molecules that are reacting and interacting with each other. However, we also know that a molecule is not alive and that a chemical reaction is not alive. So why is it that cells and tissues are alive?

With this big scientific question in mind, in recent years, researchers in the field of synthetic biology are trying to fill this gap between life sciences and physical sciences by making the first steps towards the bottom-up development of synthetic cell-like entities, called protocells. They showed that protocells can be built from unanimated molecules and materials such as phospholipids, polymers or even inorganic nanoparticles, and can be chemically programmed to mimic basic functions of living cells such as spontaneous growth and division, phagocytosis, or gene-directed protein synthesis. While many research teams are currently focusing on increasing the levels of biofunctionality and autonomy by advancing the protocells biochemical complexity, Dr Gobbo's research aims to pioneer a new research frontier by starting to spatially organise protocells into protocellular materials (or prototissues) that are stable in water and are capable of emulating living tissues. To achieve this ambitious objective, Dr Gobbo is bringing together in an original and synergistic manner key aspects of synthetic and materials chemistry in combination with synthetic biology. More specifically, his proposed work aims to tackle the following exciting challenges of protocellular materials design and synthetic construction: 1) the development of methodologies for the assembly of protocellular materials; 2) the development of communication pathways within protocellular materials; and 3) the applications of protocellular materials in tissue-engineering and synthetic biology.

Achieving forms of fully functional, adaptive and autonomous protocellular materials endowed with a programmable rudimentary form of internalised metabolism would represent an unprecedented scientific achievement. Furthermore, the synthesis of such a form of "active matter" will substantially help bridge the gap between physical and biological sciences, and have profound technological, philosophical, and socioeconomic implications.

Researchers in synthetic biology in both academia and industry are currently focusing their efforts in solving intellectual and experimental challenges of individual protocell design and synthetic construction. However, the benefits for such an ambitious scientific goal still remain essentially unexplored ("Biology from the bottom up", Nature 2018, 563, 155.). The development of methodologies to assemble protocells into protocellular materials in a controlled manner is expected to make a major technological step forward in this emerging research field, help bridge this gap between basic and applied science, and catalyse the interest of private and public sectors.

Protocellular materials are already attracting the interest of the private sector due to the necessity of developing novel high-tech analytical systems to study them, and their potential applications in biotechnology. Dr Gobbo has already established a collaboration with FemtoTools (project partner), a Swiss high-tech company that intends to expand its commercial interests and R&D portfolio in the field of soft materials. Through this partnership Dr Gobbo and FemtoTools will develop the first methodologies to characterise the micromechanical properties of protocellular materials (Case for Support, Part 2 WP1). This international collaboration will ultimately help solidify the UK's leading role in the field of synthetic biology.
In the long term (10 years from now), the development of protocellular materials endowed with a rudimentary form of programmable internalised metabolism and capable of information processing tasks will have a much broader scientific and socioeconomic impact, due to their potential applications for example on the healthcare, pharmaceutical, and environment sectors. In fact, Samsung UK (Dr Aurelien Leguy, Innovation Manager) and Astra Zeneca (Dr Samantha Peel, Associate Principal Scientist) recently expressed interest on Dr Gobbo's proposed research. For example, Astra Zeneca is interested in the potential use of this novel biomaterial for the development of bioactive membranes for blood filtration, or as a multicompartmentalized micro-bioreactor for the synthesis of proteins of interest. Concerning the environmental sector, Dr Gobbo envisions for example the possibility of using the protocellular materials for the selective removal of toxins and pollutants from contaminated waters. To implement the impact of the proposed research in the private sector, Dr Gobbo will employ the excellent support structures provided by UoB, such as the Centre for Public Engagement (R. Robinson and D. Smart) and the Research and Enterprise Development's (RED) Research Commercialisation Division (R. Darby) (Pathways to Impact).

Finally, we are acutely aware of the importance of raising public awareness of the benefits of synthetic biology. With the rapid development of this scientific field, it is natural for the public to be concerned over the philosophy and safety surrounding this research. Hence, it is important to initiate and sustain conversations with the people living and working in the community outside UoB, in order to positively shape our research. To achieve this goal the PI and the PDRA will work together with the UoB Centre for Public Engagement (Rosa Robinson and Ellie Cripps) to disseminate the outcomes to the general public (see Pathways to Impact).

To conclude, the proposed research is ambitious, adventurous and highly multidisciplinary, and will predominantly have an impact on the EPSRC Physical Sciences Theme, and especially on the growing research areas in Synthetic Biology, Chemical Biology and Biological Chemistry, and Biomaterials and Tissue Engineering. In the long-term, the proposed research is expected to have a substantial impact on the broader UK economic marketplace through an increased capacity for the development of innovative technologies in the high-tech analytical systems, tissue engineering, and biotechnology sectors.