Centre for Engineering Biology

Centre Seminar Series

Invited external speakers

 Questions?

2024 Programme

 

 Easter Holiday break 

 

Thursday 25 April 2024 - Paul Hudson (KTH Royal Institute of Technology, Sweden)

Title: Systems biology for increasing chemical production in cyanobacteria

Speaker: Paul Hudson (Head of Division of Systems Biology, KTH Royal Institute of Technology, Sweden)

Time: 9.30am - 10.30am

Format: In person

Host:   Alistair McCormick (School of Biological Sciences)

Abstract: I will describe our approaches toward optimizing photoautotrophic cyanobacteria for synthesis of chemicals from carbon dioxide. This includes first the use of CRISPR interference genetic screens to identify useful regulation points to divert fixed carbon away from growth and instead toward chemical production. Such screens have also been useful for mapping gene fitness in cyanobacteria in various growth conditions and informing on function of hypothetical genes. In a second track, we have adapted chemoproteomics methods to identify metabolite-protein interactions in the proteomes of cyanobacteria and chloroplasts, with the motivation that accumulating metabolites in genetically modified producer strains may negatively affect enzyme activity. These techniques allow us to map metabolite-protein binding surfaces. In an initial application, we found widespread interaction of tested metabolites with enzymes in central carbon metabolism, but only a fraction of these interactions affect catalysis. Finally, I will describe efforts in mutagenizing enzymes to reduce sensitivity to metabolite regulation, by high-throughput screening of the effect of enzyme mutation on both cell growth and product synthesis rates.

Thursday 9 May 2024 @3pm - Mark Ashe (University of Manchester)

Title: Orchestrated localisation and translation of functionally related mRNAs to translation factories: roles in glycolytic regulation, inheritance of the translation machinery and protein complex assembly

Speaker: Mark Ashe (Professor of Cell Biology, University of Manchester)

Time: 3pm - 4pm

Format: In person

Host:   Edward Wallace (School of Biological Sciences)

Abstract: Across many biological systems, mRNA localisation and translation form part of a strategy allowing polarised protein production. However, recent research in our laboratory shows that mRNAs encoding proteins that are not necessarily thought of as polarised are also translated at discrete sites within the cell. For instance, functionally related mRNAs such as the glycolytic and translation factor mRNAs are co-localised and translated at such sites. We and others have termed such sites translation factories,

Such co-ordinated localisation and translation of mRNAs could have a range of potential functions. Our recent published data suggests roles in the regulation of metabolic pathways and the inheritance of key proteins.  It is also possible that co-localisation of mRNAs to translation factories could have implications in the formation of protein complexes since individual components of protein complexes would not need to locate each other within a sea of macromolecules.  We have developed a proteomic approach to isolate nascent chains and their associated proteins and identify signatures of co-translational assembly. This screen identifies most of the known examples of co-translational assembly in yeast, as well as highlighting numerous other potential examples with functions across cell biology. Understanding the requirements for forming translation factories and the extent of co-translational complex production within them could therefore provide vital information regarding protein complex activity and the influences of inappropriate formation of protein aggregates.

Thursday 23 May 2024 - Benjamin Blount (Nottingham)

Title: Building and exploiting synthetic yeast genomes

Speaker: Benjamin Blount ((Assistant Professor, Faculty of Medicine & Health Sciences, University of Nottingham)

Time: 9.30am - 10.30am

Format: In person

Host:  Giovanni Stracquadanio (School of Biological Sciences)

Abstract: The international Sc2.0 project is building the first synthetic eukaryotic genome. By designing, assembling and debugging DNA on a genomic scale, we have refined our understanding of how genomes work, developed new technologies and imbued cells with new abilities. The most prominent of these abilities is SCRaMbLE, a system that rearranges synthetic chromosomes on-demand. Using SCRaMbLE, we can generate a massive amount of genotypic and phenotypic diversity from which individuals with enhanced characteristics can be identified.

In this talk I will discuss the process of building an Sc2.0 synthetic chromosome (synXI); the convoluted and at times surprising ordeal of debugging synXI; steps towards building the next generation of synthetic chromosomes; and the use of SCRaMbLE to rapidly generate strains with improved production of high value compounds, growth in new carbon sources and tolerances to a range of different stresses.  

Thursday 6 June 2024 - Jane Usher (Exeter University)

Title: A powerhouse for resistance: Candida glabrata

Speaker: Jane Usher ((BBSRC Discovery Fellow, University of Exeter)

Time: 9.30am - 10.30am

Format: In person

Host:   Peter Swain (School of Biological Sciences)

Abstract: to follow

Thursday 20 June 2024 - Simon Moore (Queen Mary University, London)

Title: To cell-free or not to cell-free: an emerging question for engineering biology

Speaker: Simon Moore ((Lecturer in Synthetic Biology, Queen Mary University of London)

Time: 9.30am - 10.30am

Format: In person

Host:  Lynne Regan (School of Biological Sciences)

Abstract:

The Moore cell-free synthetic biology group has a broad interest in natural product biosynthesis and antimicrobial resistance. In this talk, I aim to discuss the relative strengths and limitations of the emerging use of cell-free systems within academic and industrial engineering biology research.

First, I will share our recent research on the biosynthesis of two distinct natural product pathways where we are leveraging the strengths of both cell-free and microbial cell approaches to elucidate enzyme function, as well as engineer biosynthesis. Specifically, I will share our findings on uncovering several new enzymes involved in modified indole biosynthesis, as well as engineering over 20 new-to-nature indolocarbazole natural products, with potential applications for biomedicine or sustainable pigments.

Second, our group has a major focus on developing bacterial cell-free gene expression systems for rapid and combinatorial engineering of peptide, protein, and small molecule biosynthesis1–4, where we are collaborating with UK Health Security Agency and industry (e.g., Syngenta), for combating human and crop diseases, respectively. A significant part of the talk will discuss our recent development of using cell-free systems as a tool to elucidate antibiotic resistance in disease-causing bacteria, as well as the potential of developing non-standard antimicrobials5.

References

1.    Li, J., Kwon, Y.-C., Lu, Y. & Moore, S. J. Editorial: Cell-Free Synthetic Biology. Front Bioeng Biotechnol 9, 799122 (2021).

2.    Moore, S. J., Lai, H.-E., Li, J. & Freemont, P. S. Streptomyces cell-free systems for natural product discovery and engineering. Nat. Prod. Rep. (2022) doi:10.1039/d2np00057a.

3.    Nagappa, L. K. et al. A ubiquitous amino acid source for prokaryotic and eukaryotic cell-free transcription-translation systems. Front. Bioeng. Biotechnol. 10, 992708 (2022).

4.    Moore, S. J. et al. A Streptomyces venezuelae Cell-Free Toolkit for Synthetic Biology. ACS Synth. Biol. 10, 402–411 (2021).

5.    Chengan, K. et al. A cell-free strategy for host-specific profiling of intracellular antibiotic sensitivity and resistance. npj Antimicrobials and Resistance (2023) doi:10.1038/s44259-023-00018-z.