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The Sweet Road to Synthesis of Important Bacterial Sugar Structures

  • Full or part time
  • Application Deadline
    Friday, September 20, 2019
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Some of the most useful glycan structures in nature contain acidic sugars, and bacteria are often utilized as a vast resource of acidic sugar substrates. The bacterial species, Acinetobacter baumannii, is of particular importance as it is able to produce sugars belonging to the non-2-ulosonic acid (NulO) family of nine carbon acidic sugars that have proven uses in pharmaceutical and industrial applications. These include two that our team recently discovered in the species, which we named acinetaminic acid (Aci) and 8-epiacinetaminic acid (8eAci). Despite their potential for use in the health industry, their biochemical pathways are poorly understood. This project aims to investigate the biosynthesis of Aci and 8eAci using a combination of cloning, and protein purification. These sugars are gaining international interest for the important roles that NulOs play in human applications. Thus, research outputs from this project are expected to have international impact in multiple disciplines.

The aims of the project are multifaceted and will first involve the validation of the predicted genes involved sugar biosynthesis via an in vivo approach using standard mutagenesis technologies. Sugar production following mutagenesis and complementation will be assessed by visualisation using specialised staining techniques. Experimentally validated genes will then be cloned separately into an expression vector with a C-terminal His6 tag, and expressed protein purified by Ni-affinity chromatography. Each purified protein will be incubated with cofactors and synthetic pathway intermediates, and reaction products sent for NMR to confirm structures produced by each reaction. The project also has the capacity to incorporate bioinformatics techniques to identify further NulOs produced by this species.

The outcomes of this project are significant and expected to provide critical insights into the synthesis of important NulO sugars, thus advancing our knowledge on how these acidic sugars can be exploited for human use in future glycoengineering applications.

Funding Notes

Australian and International applicants are eligible to apply. Selected candidates will be required to apply for competitive scholarships through the Faculty of Health, QUT and will be assisted with their applications. PhD scholarships are approx. $27 596pa for 3.5 years full time study. PhD applicants must have completed or be expected to complete a first class hons or a Masters degree (>25% research).

Demonstrated research excellence, such as academic awards, presentations and peer-reviewed publications are desirable, but not essential.

International students must meet all entry requirements for QUT View Website.

For more information about scholarships and postgraduate study at QUT View Website.

References

Kenyon JJ, Marzaioli AM, De Castro C, Hall RM (2015) 5,7-di-N-acetyl-acinetaminic acid: A novel non-2-ulosonic acid found in the capsule of an Acinetobacter baumannii isolate. Glycobiology. 25 (6): 644-654.

Kenyon JJ, Notaro A, Hsu LY, De Castro C, Hall RM. (2017) 5,7-Di-N-acetyl-8-epiacinetaminic acid: A new non-2-ulosonic acid found in the K73 capsule produced by an Acinetobacter baumannii isolate from Singapore. Sci Rep. 7: 11357.

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