Periodic Reporting for period 2 - NANOCELL (A DNA NANOtechology toolkit for artificial CELL design)
Período documentado: 2021-07-01 hasta 2022-09-30
Artificial cells, are typically constructed from the bottom-up, starting from non-living molecular components that make up their structural elements (e.g. artificial membranes) and give them the ability to respond to stimuli. Most often scientists constructing artificial cells borrow molecular components from biological ones, using them for the same purpose for which they had evolved in the first place. While very powerful, this approach is somewhat limited, as nothing forbids us from including non-biological and non-natural components in artificial cells, which can further expand their range of capabilities and afford overall better control on their responses.
NANOCELL aims to construct artificial cells almost entirely reliant on non-biological, synthetic DNA nanostructures, utilising the tools developed in the now well-established research field of DNA nanotechnology. This approach sees DNA as a building material, rather than a genetic element, and exploits the selectivity of base-pairing to construct nanoscale objects of very well-defined structure and interactions. In our artificial cells, synthetic DNA nanostructures fulfill both structural and functional roles, roughly equivalent to what proteins do in biological cells.
A central element of the NANOCELL platform are membrane-less organelles self-assembled from DNA nanostructures. These will enable to segregation of responsive elements in different environments within each artificial cells, a key pre-requisite for building complex responses.
Over the second year of the project, we have further consolidated the structural work carried out in year one, accumulating final data which are currently being collated in multiple manuscripts which will be submitted over the course of year 3. We have also introduced a new concept for sculpting the internal structure of DNA-based synthetic cells, which relies on the design reaction diffusion processes to create organelle-like micro-environments in the cells. These findings have been shared with the community through a pre-print, and submitted to a peer-reviewed journal.
We are currently working to embed new functionalities for the artificial organelles, which will in turn allow us to engineer complex behaviours in the artificial cells. These include the ability to respond to a large number of environmental stimuli, that of synthesising, capturing and releasing molecular cargoes, and of triggering the self-assembly of other types of nano-structures which will play a functional role in the constructed artificial cells.
This toolkit will allow us to prescribe complex behaviours such as environmental sensing, communication with biological and artificial cells, information processing, synthesis/capture/release of functional molecular cargoes. Importantly this range of responses will be controllable via the modular combination of DNA-based organelles, each designed to perform specific tasks and interacting with other organelles to produce complex emergent functionalities.