Synthetic Biology and Tissue Engineering

Biography:

Harvey Coates, AO is a Paediatric Otolaryngologist and Clinical Professor in the School of Pediatrics and Child Health at the University of Western Australia. He trained at the Mayo Clinic, USA and has several research degrees and over 100 publications. His research is in otitis media in Aboriginal children and his team discovered the first middle ear biofilm as well as intracellular bacteria and NETs in the middle ear. His most recent research has been to trial tissue engineered myringoplasty in children, a major issue in Australia where over 100,000 people have chronic suppurative otitis media (CSOM). He has been awarded many community honours for his work with Aboriginal children's ear disease.

Abstract:

Background: A traumatic tympanic membrane perforation (TMP) often regenerates spontaneously, but only heals in two layers, where the absence of the central, firm and elastic layer can lead to retraction pockets and cholesteatoma. The currently available myringoplasty requires theatre time, sophisticated equipment and general anesthetic. Furthermore, outcomes are variable and inconsistent. Thus, new strategies in reconstruction of TM are desperately needed.

Objective: To evaluate the safety and efficacy of new tissue engineering myringoplasty techniques using basic fibroblast growth factor (b-FGF) alone, or in combination with a variety of scaffolds, in adults and children.

Methods: This is a prospective cohort study, designed into 4 groups: topical use of b-FGF alone; topical use of b-FGF in combination with gelatin sponge (Gelfoam^®); topical use of b-FGF in combination with silk fibroin scaffold (TymPaSil^®) and; topical use of b-FGF in combination with collagen scaffold (Celgro^®). To date, 18 adults and 12 children have been recruited from the Otolaryngology Departments of two major Western Australian Hospitals. Patients were randomized in the first 3 groups, being the latter (Celgro^®) in final stage of safety assessment. The procedure is a modification of the technique devised by Kanemaru, et al. The surgeries were performed under local anesthesia in adults and under general anesthesia in children. Serial video-otoscopy and audiometry was performed post-operatively and outcomes and results determined. Inclusion suitability for the study involved the application of defined inclusion and exclusion criteria and informed consent.

Results: Overall there was a success rate in patient terms of 83%, with the success rate in children similar. However, in terms of treatment, the children required 1.3 treatments, on average, and the adults 1.0. The major reason for the reduction in the success rate in children was related to post-operative infection or non-compliance with water precautions. In those patients with pre-operative hearing loss there was a 90% improvement in hearing. There was no safety issues related to the procedure.

Conclusion: We are reporting the safety and efficacy of b-FGF combined with different scaffolds, in an effective and short procedure with comparable success to conventional myringoplasty, in both adults and pediatric patients.

Biography:

Sharon Mendel Williams joined Coventry University as a Lecturer in the School of Life Sciences in the year 2014. She has worked as a Post-doctoral Research Fellow in both departments of Chemistry and Biology, Warwick University. Her research focuses on biophysics and biochemistry of proteins, and understanding the mechanisms of enzymes. She has a wide range of experience in molecular biology, biochemistry, and chemistry. She is a member of the Royal Society of Chemistry and has been awarded a grant from the RSC research fund to accomplish her research work

Abstract:

A project in bioinformatics will significantly increase the portfolio of skills in science research on top of an already extensive set of laboratory skills you have achieved until now. The twin arginine transport (Tat) system transports folded proteins across bacterial and thylakoid membranes. In gram-negative organisms, it is encoded by tatABC genes and the system recognizes substrates bearing signal peptides with a conserved twin-arginine motif. Most gram-positive organisms lack a tatB gene, indicating major differences in organisation and/or mechanism. The essential targeting determinants that are recognized by a Bacillus subtilis TatAC-type system, TatAdCd have been characterized. Substitution by lysine of either of the twin-arginine residues in the TorA signal peptide can be tolerated, but the presence of twin-lysine residues blocks export completely. The DmsA signal peptide (sequence SRRGLV) appears to play an equally important role and substitution by alanine or phenylalanine blocks export by both the B. subtilis and E. coli systems. These data identify three distinct determinants, whose importance varies depending on the signal peptide in question. The data also show that the B. subtilis TatAdCd and E. coli TatABC systems recognize very similar determinants within their target peptides, and exhibit surprisingly similar responses to mutations within these determinants. In the current project you will use bioinformatics in order to find other signal peptides that can be used by the Tat systems and you will use different prediction methods and compare the results.