Mark Isalan carried out a Ph.D. in engineering zinc fingers to bind new DNA sequences at the MRC LMB, in the University of Cambridge UK,1996-2000. This work was supervised by Prof. Sir Aaron Klug, OM, FRS, and continued postdoctorally from 2000-2002 at Gendaq Ltd, UK (now owned by Sangamo Biosciences, Richmond CA). The work ultimately contributed to the CompoZr zinc finger nucleases now available commercially from Sigma Aldrich. From 2002-2006 Dr. Isalan was awarded a Wellcome Trust International Research Fellowship to carry out research on engineering artificial gene networks in Prof. Luis Serrano's group at the EMBL Heidelberg, Germany. From 2006-2013 he was a group leader at the EMBL-CRG Systems Biology Unit in Barcelona, specialising in synthetic gene network engineering. He moved to Imperial College London in 2013 and continues to work in protein and gene network engineering, aiming to design biological systems that behave predictably and robustly.
Mycoplasmas have exceptionally streamlined genomes and are strongly adapted to their many hosts, which provide them with essential nutrients. Owing to their relative genomic simplicity, Mycoplasmas have been used for the development of chassis to deploy tailored vaccines. However, the dearth of robust and precise toolkits for genomic manipulation and tight regulation has hindered any substantial advance. Here, we describe the construction of a robust genetic toolkit for M. pneumoniae, and its successful deployment to engineer synthetic gene switches that control and limit Mycoplasma growth, for biosafety containment applications. We found these synthetic gene circuits to be stable and robust in the long-term, in the context of a minimal cell. With this work, we lay a foundation to develop viable and robust biosafety systems to exploit a synthetic Mycoplasma chassis for live attenuated vaccines or even for live vectors for bio-therapeutics.
For details of his research and recent publication, please visit HERE.
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