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Current Research Projects

 

 

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Overview: Our laboratory conducts research on fungal systems, but also on the biochemical mechanisms that fungi use to cause disease or to deconstruct/decay lignocellulose biomass. The groups of fungi we work with employ unique, and very interesting, redox-cycling chemistries that allow these organisms to cause damage and/or initiate pathogenesis. Our research has also branched out into the study of the biochemical mechanisms that the fungi use - but in this work, we remove the organisms from the system but utilize our understanding of the biochemistries involved to mimic their action. This allows us  to study disease mechanisms more readily, or to develop "biomimetic" processes. One biomimetic process we are exploring in the lab now with an international consortium of colleagues is in the deconstruction of biomass for future "biorefinery" applications.  In other research in the biomedical realm, we are also exploring how related redox-cycling chemistries may promote neurodegenerative disease when these chemistries are triggered in specific organelles of the cell. 

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Background: Unique, Non-Enzymatic Extracellular Mechanisms in Fungi

Many groups have studied the enzymes and extracellular enzymatic action of fungi and other microorganisms. Our research group has interest in several enzymatic systems, but our primary focus is on non-enzymatic extracellular systems that some fungi employ, either alone, or in conjunction with enzymatic activities. Enzymes are large molecules that contain large amounts of nitrogen. From the physiological perspective, it is very expensive for an organism to produce and secrete enzymes extracellularly because those enzymes may not be readily recoverable by the organism. Some fungal organisms have evolved to produce a non-enzymatic redox-cycling system utilizing low molecular weight compounds that have the ability to perform simple catalytic chemistries that substitute for enzymatic action. One such catalytic chemistry is the generation of hydroxyl radicals (•OH) using what is know as a "chelator-medicated Fenton" (CMF) system. The (•OH) radical is the most potent oxidizing agent known in biological systems, and much of our research focusses on how fungi are able to generate these radical species "at a distance" from the fungal hyphae to cause diseaseor to degrade various substrates (ranging from wood to xenobiotic pollutants).  The (•OH) radicals must be generated far enough away from the fungus so that the fungal organism is not damaged, but by producing such a system that carries out the function of extracellular enzymes in other systems, we believe that physiological expense is greatly reduced, thus conferring an evolutionary advantage to fungi that use such systems.  

Image courtesy of Jim Conrad

CDC/ Dr. Leanor Haley

Deconstruction by BR Fungi

Cryptococcus spp. in yeast form invading the brain in fish (Duke Univ image)Cryptococcus causes 600,000 human deaths each year globally.

Video Anchor
Video by Professor Barry Goodell. Jackson Lab STED Microscopy

Video Caption: Below is a high resolution image taken using a new type of microscopy known as Stimulated Emission Depletion (STED) or 4Pi microscopy. Stefan W. Hell shared the 2014 Nobel Prize in Chemistry for the discovery of 4Pi physics which permits "super resolution" imaging of living cells.  This is a video of fungal "clamp connection" from Gloeophyllum trabeum , a unique fungus which has developed a non-enzymatic mechanism that can deconstruct diverse polymers in nature, but its preferred substrate is wood. Here, we are able to resolve down to approximately 50 nm in a living G. trabeum hyphal segment, growing inside a wood tracheid. Organelle structure can be observed as we digitally slice though the hyphal segment.

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