Dr Jan Schmid's Research Interests
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I) Molecular Microbiology of Candida albicans
The yeast C. albicans is found in most humans as a harmless commensal organism. Millions of yeast cells can be present in an individual without any ill effect. However C. albicans is also the major fungal pathogen of humans. Infections can be localized, such as vaginal infections and oral infections, which cause a considerable degree of discomfort. In patients with a compromised immune system (prematurely born infants, leukemics and burn patients), the yeast can turn into a deadly pathogen, causing disseminated infections; up to 50% of the infected patients die as a result. The incidence of such infections is increasing. In New Zealand, they are now ten times more frequent than they were 15 years ago. Our reservoir of anti-Candida drugs is very limited. Development of new strategies for the prevention and treatment of candidiasis is therefore probably the most important challenge faced by medical mycology today.
Some key findings from our work:
Theoretical considerations predict that general-purpose genotypes can only survive in the absence of sexual recombination (Schmid et al., 2004). C. albicans was long considered asexual. But it has recently been discovered that it is in principle still capable of limited sexual recombination. A Marsden grant from the Royal Society of New Zealand has allowed us to launch an investigation aimed at determining if sex still has adaptive value for the species.
Some key findings from our work:
- Not all C. albicans strains are equally likely to cause disease. We have identified a general-purpose genotype (GPG), that causes disease significantly more often than other genotypes (Schmid et al., 1999) and is also more virulent in human patients (Schmid et al, 2011).
- Part of the differences between GPG strains and other strains occur in so-called hypermutable contingency genes. We identified sixty different alleles of one of these genes, ALS7(Zhang et al., 2003).
Theoretical considerations predict that general-purpose genotypes can only survive in the absence of sexual recombination (Schmid et al., 2004). C. albicans was long considered asexual. But it has recently been discovered that it is in principle still capable of limited sexual recombination. A Marsden grant from the Royal Society of New Zealand has allowed us to launch an investigation aimed at determining if sex still has adaptive value for the species.
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A neighbor-joining tree of 300 C. albicans isolates shows that a cluster of genetically highly similar strains causes 40% of all infections (Schmid et al., 1999). |
II) Molecular Microbiology of Neotyphodium endophytes
Neotyphodium endophytes are fungal symbionts within the intercellular spaces of grass plants, which enhance plant resilience and resistance against insects and nematodes. The presence of the endophyte also induces the formation of compounds, which are toxic to grazing livestock. It is therefore of agricultural importance to determine how the latter effect can be minimized while maintaining the agriculturally beneficial aspects of the symbiosis. In addition the symbiosis is a likely source of novel bioactive compounds with applications in biotechnology and medicine.
Some key findings from out work to date:
Some key findings from out work to date:
- The growth of the endophyte is highly synchronized with that of the plant (Tan et al.,2001).
- The host's pathogen response may play a role in establishing a functional symbiosis (Zhang et al., 2011).
- Unlike in culture, nongrowing endophyte hyphae in plants maintain very high metabolic rates (Tan et al.,2001).
- The correlation between the distribution of endophyte biomass and alkaloid distribution in planta is poor, highlighting the importance of gene regulation and transport in determining alkaloid levels (Spiering et al., 2005).
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Two-dimensional electrophoresis of protein extracts from infected and uninfected ryegrass plants is one of the tools we use for characterizing the interaction between endophyte and grass. The image shows three proteins detectable only in endophyte-infected ryegrass tissue. Proteins k1 and k2 belong to a family of highly conserved proteins (PR-10 proteins) which form part of the response to plants to pathogens. Protein k8 is a N. lolii superoxide dismutase, highly expressed in plants but not when the fungus is grown in culture (Zhang et al., 2011). |
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III) Molecular epidemiology of bacterial pathogens
Dating back to the development of the computer-assisted Ca3 typing technology for C. albicans (Schmid et al., 1990), we have a long-standing interest in the development and innovative application of molecular typing technologies for epidemiological research. We have applied this expertise to a number of bacterial pathogens. Two highlights from this work are the discovery of ethic tropism in Helicobacter pylori (Campbell et al., 1997), and the discovery that transmission of Pseudomonas aeruginosa is comparatively rare among New Zealand cystic fibrosis patients (Schmid et al., 2008).
