[Dr.J. David Miller] [Research][Publications] [ResearchTeam] [ContactInformation]
The motivating scientific interest of my research is the role of fungal metabolites in determining population structure. I became interested in this during my postdoctoral work where I observed that distributions of marine fungi on wood seemed to be partially determined by the production by some species of anti-fungal metabolites.
Few academic research programs in North America work in the area of natural products from fungi and the program produces highly qualified personnel that will be able to seek careers in the pharmaceutical and environmental industries. This effort reflects also the Canadian Government priority to engage more scientists outside medical schools in the problems of medical research.
There are three lines of research conducted in the Miller laboratory. Thefirst area of research is into the link between damp housing andhealth. The second area is the role of endophyticfungi in conifer needles. Thirdly we conduct research on toxinsin food.
Damp Housing and Health
|Canadians spend 92% of their time indoors. Between 10 and 30% of homes in Canada have moisture problems. This means that occupants are breathing large numbers of fungal spores not found in outdoor air. Such spores contain largely unknown allergens and toxins, including spore-specific toxins. Panels of the US National Academy of Science (2000, 2004) and Health Canada (2004) commented on the health effects of mold in buildings. In 2007, Health Canada issued a guideline for residences on the presence of mold. A panel organized by the US Center for Healthy Housing and the US CDC found that there was public health evidence for the removal of mold and the elimination of the underlying moisture problem. The effect is apparently due to both low molecular weight compounds (toxins) and allergens. It is currently impossible to measure personal exposures to fungi in buildings for epidemiological studies and other purposes. This is because existing methods are not sufficiently sensitive and measure proxies for the biologically active fungal compounds. The prevalence of allergic diseases due to fungi is underestimated because of the lack of appropriate diagnostic tools.
We have two broad goals. Working with a large clinical laboratory in the USA, we have access to sera of atopic patients from which we can mine human antigens. Human antigens will be characterized and then be used to develop antibody-based methods for the quantitative determination of fungi in indoor air including of personal exposure. This will strengthen epidemiological studies done in Canada and elsewhere and determine whether the associations described between fungi and health are causal and determine the attributable risk (disease burden). This will permit the development of better public policy with respect to damp housing, schools and other public buildings. This will also revolutionize the practice of measuring fungi in indoor air for industrial hygiene purposes and permit the accurate diagnosis of building exposures associated with building-related illness. The outcome of the work will have a major impact in terms of preventing such illnesses and the reduced productivity associated with buildings with mold problems. So far, we have identified a number of useful antigens from the indicator species Stachybotrys chartarum sensu latto, Penicillium. chrysogenum clade 4 and A. versicolor and created mAb-based tests. Fungi under study at present include Wallemia sebi and Chaetomium globosum.
A second goal is to determine the
spore-bore toxins of building-associated fungi and effects of such toxins on
lung biology. We have characterized the toxins from number fungi from damp
buildings describing new compounds and producing pure toxins. Along with the
form of beta 1, 3, D glucan found in fungi found in the built environment, these
have been studied for their effects on effect on lung biology. Prof. Tom Rand
(St. Mary’s) and our group have collaborated on studies that have shown that in
rodent models including primary alveolar cell cultures very low doses, the
transcription and expression of genes involved in immunological responses. There
are different patterns of response of various toxins which are in turn different
than those of glucan. For the first time, this has identified a partial
mechanistic basis for the toxic effect on population noted above.
Endophytic Fungi in Conifer Needles
|Considered over the past 50 years, the eastern spruce budworm is easily the most economically-damaging insect pest in Canada. The last time there was an epidemic, large scale spraying of a hard chemical pesticide was undertaken. Where this was not done, the forests were devastated. Over the intervening two decades, during a low period of the budworm cycle, the hard chemical pesticides used in the 1970’s were de-registered in favour of more expensive and less effective biopestices. Regardless, it less likely now that the social consensus would exist for the widespread use of a hard chemical insecticide when the spruce budworm population returns to epidemic proportions.
We have shown that some strains of
white spruce needle endophytes (fungi that live inside the leaves),
produce compounds that affect the survival of the spruce budworm. They are
horizontally transmitted which has the effect of reducing diversity of
endophytes on former agricultural or harvested lands whether by natural
regeneration or planting seedlings. The needles of seedlings colonized by
“good” endophytes contain anti-insect toxins and the growth rate and
resistance to parasites and natural bacterial pathogens are both reduced.
We have been able to successfully infect seedlings on a large scale. The
fungi are persistent in the tree over many years (>8) and when present on
trees infected with these natural toxin-producing endophytes, spruce
budworm do not grow as fast. As more re-forestation is done with seedlings
infected by good endophytes, this is expected to produce forests more
resistance to herbivorous insects and lessen the need for interventions
such as spraying in the future. In the past few years, there have been
studies of pine endophytes in relation to their role in increasing
tolerance to white pine blister rust, a fungal disease that is very
serious in western Canada and has been present at a low level in eastern
Canada for many years. We have found strains that produce compounds that
are known to affect rust growth in vitro.
Toxins in Food
Exposure to mycotoxins present in food and feed crops has long been recognized as a serious threat to human and animal health. And, according to a 1996 United Nations report, “Freedom from mycotoxins in food ... is an indicator of sustainable development. Mycotoxins are chemicals that are produced in food and feed by fungi that grow on crops either in the field or in storage. In much of the developing world, two important crops are commonly contaminated: maize and groundnuts – major food crops and cash earners for millions of small-scale farmers. The best known of these chemical substances is aflatoxin, produced by Aspergillus flavus, found in both maize and groundnuts. In Canada, the Fusarium toxin deoxynivalenol is the most important. More recently, fumonisin, produced by Fusarium verticilliodes, was discovered in maize in southern Africa but is found in warm areas wherever corn is grown.
As part of a collaboration with
Prof Art. Schaafsma (Guelph), we have worked on models for the
accumulation fumonisin in corn as well as the concentration of
deoxynivalenol in feeds arising from the production of fuel ethanol.
[Dr.J. David Miller] [Research][Publicaions] [Research Team] [ContactInformation]