Kim Miles - Publications

Journal Publications

5. Miles KM, Miles JJ, Madura F, Sewell AK, Cole DK. (2010 Dec 2) Real time detection of peptide-MHC dissociation reveals that improvement of primary MHC-binding residues can have a minimal, or no, effect on stability. Mol Immunol Vol 48, Issue 4, pg 728-32.

4. Marion Tarbe, Itxaso Azcune, Eva Balentov´a, John J. Miles, Emily E. Edwards, Kim M. Miles, Priscilla Do, Brian M. Baker, Andrew K. Sewell, Jesus M. Aizpurua, C´eline Douat-Casassus and St'ephane Quideau. (2010 Sep 2) Design, synthesis and evaluation of b-lactam antigenic peptide hybrids; unusual opening of the b-lactam ring in acidic media. Organic and Biomolecular Chemistry.

3. Linden SK, Sheng YH, Every AL, Miles KM, Skoog EC, Florin TH, Sutton P, McGuckin MA. (2009 Oct 5) MUC1 limits Helicobacter pylori infection both by steric hindrance and by acting as a releasable decoy. PLoS Pathog.

2. Lindén SK, Driessen KM, McGuckin MA. Improved in vitro model systems for gastrointestinal infection by choice of cell line, pH, microaerobic conditions, and optimization of culture conditions. Helicobacter. 2007 Aug;12(4):341-53.

1. Martin S, Driessen K, Nixon SJ, Zerial M, Parton RG. Regulated localization of Rab18 to lipid droplets: effects of lipolytic stimulation and inhibition of lipid droplet catabolism. J Biol Chem. 2005 Dec 23;280(51):42325-35. Epub 2005 Oct 5.

Conference Presentations

Australian Society of Microbiology 2007>br /> 10 min talk from the abstract:
Microaerobic Co-culture of Gastrointestinal Mucin Producing Cells with Campylobacter jejuni

Kim M Driessen, Michael A. McGuckin and Sara K Lindén
Mucosal Diseases Program, Mater Medical Research Institute, Level 3 Aubigny Place, Raymond Terrace,
South Brisbane, QLD 4101, Australia.

Mucins are highly O-glycosylated proteins found on the intestinal surface creating a protective barrier. Bacteria of the gastrointestinal tract (GIT) bind to, and exhibit chemotaxis to certain mucins. Despite the importance of mucin-bacteria interactions, current in vitro models use cell lines that have not been selected for appropriate mucin expression. Furthermore, these models often fail to mimic microaerobic conditions found in the GIT. To make in vitro studies more applicable to human disease we have developed co-culture methods taking these factors into account.

Nine human gastrointestinal epithelial cell lines (MKN1, MKN7, MKN28, MKN45, KATO3, HFE145, PCAA/C11 Caco-2 and LS513) were investigated. Expression and glycosylation of mucins (MUC1, 2, 3, 4, 5AC, 5B, 6, 12, 13 and 16) were determined by immunohistochemistry. The cell lines varied in mucin expression with MKN7 and MKN45 being most similar to gastric mucosa and Caco-2 and LS513 to intestinal mucosa, although none exactly matched normal mucosa.

Microaerobic culture did not adversely affect mammalian cell viability, proliferation or induce apoptosis. C.jejuni co-cultured with the intestinal cell line LS513 increased in number with time, and approximately 2- fold more C. jejuni were recovered from microaerobic conditions than from aerobic conditions. Additionally, the majority of samples displayed a swarming phenotype on agar (which is necessary for in vivo colonisation), whereas swarming did not occur in bacteria cultured under aerobic conditions. Furthermore, under microaerobic conditions, C. jejuni producing cytolethal distending toxin (CDT) trigger G2 arrest in up to 70.4% of LS513 cells in a dose dependent manner. Thus, microaerobic culture conditions do not adversely effect the mammalian cells, and creates physiological growth conditions for the bacteria. The development of a practical and efficient model for microaerobic culture of intestinal cells with bacteria provides a tool to more accurately investigate effects of bacterial interactions with intestinal cells.