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Prof M X Caddick
Prof A Darby
Applications accepted all year round
About the Project
1. Determine key transcript features associated with RNA stability and translational efficiency.
2. Incorporate findings in design of genes to optimise expression of extracellular enzymes.
RNA stability and translational efficiency are key determinants of protein expression which have a significant impact on enzyme production. mRNA levels only partially reflect protein expression, with translational efficiency varying by over 100 fold, and transcript half lives vary dramatically in fungi, ranging from 3 minutes to over 100 minutes. Both translational efficiency and RNA stability can be subject to regulation and are programmed into the transcripts. This project will aim to investigate the transcripts features, which impact on expression. Gene expression data from RNAseq and published microarray experiments will be used to identify transcripts which display high RNA levels, stability and/or translational efficiency (as determined by polysome association or proteomics data). Bioinformatic analysis will be utilised to identify enrichment for specific features (codon usage, presence/absence of polynuclotide runs, short/long UTRs, sequence motifs or 2’ sequence structures). The sequence features identified will be investigated both by mutational analysis of the respective transcripts and inclusion in reporter constructs. Comparative genomic analysis will be utilised to map the conservation of these elements across species. Key features will then be tested using synthetic gene constructs both in A. nidulans and strains of industrial relevance such as A. niger or M. thermophila C1. This project is part of a collaboration with Dyadic Netherlands, a biotechnology company based in Holland. The key aim is to enhancing expression of novel extracellular enzymes.
Training:
The candidate will receive a broad training in both Bioinformatics, including the handling of large data sets and their computational interrogation, and molecular genetics, developing expertise in working with model microbial systems. This will include training in the analysis of mRNA modification and degradation, directed gene disruption, tagging and mutagenesis, protein characterisation and phenotypic analysis. There is a possibility for interaction with industrial collaborators. A broad generic training program is also in place for postgraduate students ranging from Bioinformatics through to intellectual property and business.
2. Incorporate findings in design of genes to optimise expression of extracellular enzymes.
RNA stability and translational efficiency are key determinants of protein expression which have a significant impact on enzyme production. mRNA levels only partially reflect protein expression, with translational efficiency varying by over 100 fold, and transcript half lives vary dramatically in fungi, ranging from 3 minutes to over 100 minutes. Both translational efficiency and RNA stability can be subject to regulation and are programmed into the transcripts. This project will aim to investigate the transcripts features, which impact on expression. Gene expression data from RNAseq and published microarray experiments will be used to identify transcripts which display high RNA levels, stability and/or translational efficiency (as determined by polysome association or proteomics data). Bioinformatic analysis will be utilised to identify enrichment for specific features (codon usage, presence/absence of polynuclotide runs, short/long UTRs, sequence motifs or 2’ sequence structures). The sequence features identified will be investigated both by mutational analysis of the respective transcripts and inclusion in reporter constructs. Comparative genomic analysis will be utilised to map the conservation of these elements across species. Key features will then be tested using synthetic gene constructs both in A. nidulans and strains of industrial relevance such as A. niger or M. thermophila C1. This project is part of a collaboration with Dyadic Netherlands, a biotechnology company based in Holland. The key aim is to enhancing expression of novel extracellular enzymes.
Training:
The candidate will receive a broad training in both Bioinformatics, including the handling of large data sets and their computational interrogation, and molecular genetics, developing expertise in working with model microbial systems. This will include training in the analysis of mRNA modification and degradation, directed gene disruption, tagging and mutagenesis, protein characterisation and phenotypic analysis. There is a possibility for interaction with industrial collaborators. A broad generic training program is also in place for postgraduate students ranging from Bioinformatics through to intellectual property and business.
Funding Notes
This project may be eligible for a BBSRC studentship which is available to students from the UK (stipend and fees) or EU (fees only). Alternatively the project will have to be self funded or for those with an appropriate fellowship. This project may be eligible for a BBSRC studentship which is available to students from the UK (stipend and fees) or EU (fees only). Alternatively the project will have to be self funded or for those with an appropriate fellowship.
References
Morozov, I.Y., Jones, M.G., Razak, A.A., Rigden, D.J., and Caddick, M.X. (2010). CUCU modification of mRNA promotes decapping and transcript degradation in Aspergillus nidulans. Mol. Cell Biol. 30:460-469.
Morozov IY, Jones MG, Spiller DG, Rigden DJ, Dattenbock C, Novotny R, Strauss J and Caddick MX. (2010). Distinct roles for Caf1, Ccr4, Edc3 and CutA in the coordination of transcript deadenylation, decapping and P-body formation in Aspergillus nidulans. Molecular Microbiology 76:503-516.
Caddick M X, Jones M G, van Tonder J M, Le Cordier H, Narendja F, Strauss J and Morozov IY. (2006) Opposing signals differentially regulate transcript stability in Aspergillus nidulans. Mol. Microbiol. 62:509-519.
Morozov IY, Jones MG, Spiller DG, Rigden DJ, Dattenbock C, Novotny R, Strauss J and Caddick MX. (2010). Distinct roles for Caf1, Ccr4, Edc3 and CutA in the coordination of transcript deadenylation, decapping and P-body formation in Aspergillus nidulans. Molecular Microbiology 76:503-516.
Caddick M X, Jones M G, van Tonder J M, Le Cordier H, Narendja F, Strauss J and Morozov IY. (2006) Opposing signals differentially regulate transcript stability in Aspergillus nidulans. Mol. Microbiol. 62:509-519.
Project supervisors
Prof M X Caddick's profile is coming soon
View other supervisors at University of LiverpoolCareer overview
Professor Alistair Darby is a Co-Director of the Centre for Genomic Research at the University of Liverpool and has over 20 years of experience in microbiome and microbial/host interactions. He possesses an international track record in researching human and zoonotic pathogens and their vectors. His scientific work employs genomic techniques to unlock biological processes, integrating molecular biology, technology, and bioinformatics to enhance the understanding of host-microbe interactions. This multidisciplinary approach fosters collaboration across various research teams, with Professor Darby providing genomic expertise to support diverse biological inquiries. He obtained a B.Sc. (Hons) in Biology with a 2:1 classification from the University of York, UK, in 1997. Following this, he completed a M.Sc. (Dic) in Applied Entomology at Imperial College, UK, in 1998. Professor Darby earned his Ph.D. in 2003, focusing on aphid symbiosis under the supervision of Professor A.E. Douglas at the University of York, UK.
Research interests
Professor Alistair Darby''s research focuses on microbiome and microbial/host interactions, with a particular emphasis on human and zoonotic pathogens and their vectors. He employs genomic techniques to enhance the understanding of biology, integrating molecular biology, technology, and bioinformatics. His work is multidisciplinary and highly collaborative, aimed at elucidating host-microbe interactions. Professor Darby brings unique genomic expertise to various research teams, contributing to the understanding of diverse biological systems.
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