Controlling nucleic acid technologies
DNA and RNA form the basis for many therapeutic and experimental technologies, including gene editing and silencing, several aspects of nanotechnology, aptamers and their applications, and cell-free protein expression. It would be advantageous to control the function of these technologies, as this would greatly expand their application in biology and medicine by reducing toxic on/off-target effects and systemic toxicity. The main focus of our research is the generation of remote-controlled nucleic acids under the control of various stimuli, including temperature, magnetism, enzymes, chemical signals, and multiple wavelengths of light. These nucleic acids will be optimized to function with molecular machines, drug delivery, sensing, and siRNA and CRISPR technologies. In the future, this universal chemical method for controlling DNA and RNA structure and function may form the basis of controllable therapeutics and new technologies for basic research.
Selected publications:
Blue light-activatable DNA for remote controlled logic gates in synthetic cells. D.Hartmann, R.Chowdhry, J.M.Smith, M.J.Booth. ChemRxiv (2023) DOI:10.26434/chemrxiv-2022-p8xgb-v2
Controlling gene expression with light: a multidisciplinary endeavour. D.Hartmann, J.M.Smith, G.Mazzotti, R.Chowdhry, M.J.Booth. Biochemical Society Transactions, BST20200014 (2020) DOI:10.1042/BST20200014
Light-activated communication in synthetic tissues. M.J.Booth, V.Restrepo-Schild, A.D.Graham, S.N.Olof, H.Bayley. Science Advances, 2 (4), e1600056 (2016) DOI:10.1126/sciadv.1600056
Synthetic cells for drug delivery to natural cells
Considerable research goes into the development of exciting new molecular tools and drugs; however, a large stumbling block can be how to effectively deliver these molecules into targeted cells. We aim to utilize synthetic cells, lipid-bounded compartments containing a cell-free protein expression system inside them, for controllable and targeted drug delivery. These synthetic cells will be able to deliver a large variety of molecules, from small molecule drugs to large biomacromolecules. Through both direct and in-direct mechanisms, these synthetic cells will have the ability to deliver their contents into natural cells. Control of delivery will be achieved with the compartmentalisation of remote-controlled nucleic acids within these synthetic cells.
Selected publications:
Engineering cellular communication between light-activated synthetic cells and bacteria. J.M.Smith, D.Hartmann, M.J.Booth. BioRxiv (2022) DOI: 10.1101/2022.07.22.500923
Controlling Synthetic Cell-Cell Communication. J.M.Smith, R.Chowdhry, M.J.Booth. Frontiers in Molecular Bioscience, 8, 809945 (2022) DOI: 10.3389/fmolb.2021.809945
Multi-responsive hydrogel structures from patterned droplet networks. F.G.Downs, D.J.Lunn, M.J.Booth, J.B.Sauer, W.J.Ramsay, R.G.Klemperer, C.J.Hawker, H.Bayley. Nature Chemistry, 12, 363 (2020) DOI:10.1038/s41557-020-0444-1
Light-activated communication in synthetic tissues. M.J.Booth, V.Restrepo-Schild, A.D.Graham, S.N.Olof, H.Bayley. Science Advances, 2 (4), e1600056 (2016) DOI:10.1126/sciadv.1600056
Booth Research Group 