Progress 10/01/13 to 09/30/15
Outputs
Target Audience:Target audience has been the research community and were reached through efforts of publications and presentations at meetings. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?This project has contributed to Ms. Lim's professional and training. Ms. Lim is also mentoring an undergraduate student on research experience in the lab. Ms. Lim has presented her work at meetings. How have the results been disseminated to communities of interest?Our work is largely disseminated by publications and presentations at meetings. Meetings are typically at research conferences. What do you plan to do during the next reporting period to accomplish the goals?Our work is continued under project WIS0189. 1. Assess the role of BrlA regulated toxins on spore survival. 2. Determine the role of FleA on spore survival and if FleA is required for adhesion to host surfaces or other microbes. 3. Determine if the copper regulated cluster is important for survival 4. Hopefully we can start on laeB work in A. flavus
Impacts
What was accomplished under these goals?
Our focus was on identifying regulators of mycotoxin biosynthesis or regulation of growth of the fungi that make mycotoxins. Mycotoxins are a major type of plant disease and result in the most yield loss of any plant disease type. The mycotoxin producing fungi cause yield loss through tissue destruction and present a tremendous health problem by the production of mycotoxins in seed. Our laboratory goals are: (1) identification of regulators of mycotoxin production in Aspergillus spp and/or (2) continue progress in identifying molecules in Aspergillus to complete its disease cycle. Regarding goal 1, we have identified several global regulators of mycotoxin production . For example, a recent finding, not yet published, is a gene called LaeB that regulates sterigmatocystin production in A. nidulans. We have recently disrupted this gene in A. flavus and will be starting to work on this project once we have another graduate student in the lab. We have also found a previous characterized protein called LaeA. This protein regulates all mycotoxins in all fungi. We have recently found that LaeA regulates production of spore toxins through the transcription factor known as BrlA. BrlA was identified several years ago as a protein necessary for Aspergillus species to produce conidiophores and, hence, conidia the initial inoculum. The brlA gene is positively regulated by laeA in all Aspergillus species, we have looked (e.g. A. flavus, A. nidulans and A. fumigatus) and we have recently found that LaeA regulates brlA expression via chromatin remodeling of the brlA promoter. PhD student Fang Yun Lim has identified several spore specific toxins regulated by LaeA in A. fumigatus, which have an impact on the human immune system. She has published on some of these which canbe seen in the products section. Ms. Lim is asking if BrlA regulation of spore metabolites are important for fungal survival. Regarding goal 2, Ms Lim is now focusing on a new putative toxin cluster that might be important for copper homeostasis in A. fumigatus.A second project Ms. Lim is involved in concerns a lectin binding protein called FleA found in A. fumigatus and A. flavus. We believe that this protein is important for adhesion to host tissue or in interactions with competing microbes.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Throckmorton K, Lim FY, Kontoyiannis DP, Zheng W, Keller NP (2015) Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus. Environ Microbiol doi: 10.1111/1462-2920.13007.
- Type:
Journal Articles
Status:
Published
Year Published:
2015
Citation:
Bok JW, Wiemann P, Garvey GS, Lim FY, Haas B, Wortman J, Keller NP (2014) Illumina Identification of RsrA, a conserved C2H2 transcription factor coordinating the stress signaling pathway in Aspergillus. BMC Genomics. 15:1011.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Lim FY, Ames B, Walsh C, Keller NP (2014) Coordination between BrlA regulation and secretion of the oxidoreductase FmqD directs selective accumulation of fumiquinazoline C to conidial tissues in Aspergillus fumigatus. Cell Microbiol. 16(8):1267-83.
- Type:
Journal Articles
Status:
Published
Year Published:
2014
Citation:
Lim FY, Keller NP (2014) Spatial and Temporal Control of Fungal Natural Products Synthesis. Nat Products Reports. 31:1277-86. PMCID:PMC4162804
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Progress 10/01/13 to 09/30/14
Outputs
Target Audience: Target audience has been the research community and were reached through efforts of publications and presentations at meetings. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided? This project has contributed to Ms. Lim's professional and training. She has not only made experimental progress, but was an assistant for a mycology course which improved her teaching. Ms. Lim is also mentoring an undergraduate student on research experience in the lab. Ms. Lim has presented her work at meetings. How have the results been disseminated to communities of interest? Our work is largely disseminated by publications and presentations at meetings. Meetings are typically at research conferences. What do you plan to do during the next reporting period to accomplish the goals? Work goals 2014/2015: 1. Assess the role of BrlA regulated toxins on spore survival. 2. Determine the role of FleA on spore survival and if FleA is required for adhesion to host surfaces or other microbes. 3. Ask if any GPCR receptor is involved in recognizing quorum sensing molecules.
Impacts
What was accomplished under these goals?
Our focus was on identifying regulators of mycotoxin biosynthesis. Mycotoxins are a major type of plant disease and result in the most yield loss of any plant disease type. The mycotoxin producing fungi cause yield loss through tissue destruction and present a tremendous health problem by the production of mycotoxins in seed. Our laboratory goals are: (1) identification of global regulators of mycotoxin production in the model fungus Aspergillus nidulans as such regulators have the potential to control production of several mycotoxins across several genera and (2) continue progress in identifying both small molecules and fungal receptors in A. flavus which are required for the ability of A. flavus to complete its disease cycle. Regarding goal 1, we have identified several global regulators of mycotoxin production in A. nidulans. For example, a recent finding, not yet published, is a gene called LaeB that regulates sterigmatocystin production in A. nidulans. We have recently disrupted this gene in A. flavus and will be starting to work on this project full time in fall 2015. We have also found a previous characterized protein called LaeA. This protein regulates all mycotoxins in all fungi. We have recently found that LaeA regulates production of spore toxins through the transcription factor known as BrlA. BrlA was identified several years ago as a protein necessary for Aspergillus species to produce conidiophores and, hence, conidia the initial inoculum. The brlA gene is positively regulated by laeA in all Aspergillus species, we have looked (e.g. A. flavus, A. nidulans and A. fumigatus) and we have recently found that LaeA regulates brlA expression via chromatin remodeling of the brlA promoter. PhD student Fang Yun Lim has identified several spore specific toxins regulated by LaeA in A. fumigatus, which have an impact on the human immune system. One of them is called endocrocin and we find it is regulated by LaeA through BrlA. Ms. Lim is asking if BrlA regulation of spore metabolites are important for fungal survival. Regarding goal 2, we are focusing on a quorum sensing program in A. flavus that governs aflatoxin production, spore production and sclerotial production. In particular, we are focusing on membrane receptors in the fungus that recognize quorum molecules and we propose that G protein coupled receptors (GPCR) are the likely receptors involved in quorum sensing. Aspergillus flavus contains 16 GPCR in its genome and our lab had recently characterized two of them involved in lipid signaling. We therefore proposed to characterize the remaining 14 GPCR. This work was accomplished faster than anticipated and we have published the deletion of all 14 GPCR. We are now testing these mutants to see if they are impaired in density development. We are also interested in those genes which enable fungi to survive in their environment. A second project Ms. Lim is involved in concerns a lectin binding protein called FleA found in A. fumigatus and A. flavus. We believe that this protein is important for adhesion to host tissue or in interactions with competing microbes.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
PLoS One. 2013 Sep 9;8(9):e74030. doi: 10.1371/journal.pone.0074030. eCollection 2013.
The bZIP protein MeaB mediates virulence attributes in Aspergillus flavus.
Amaike S1, Affeldt KJ, Yin WB, Franke S, Choithani A, Keller NP.
- Type:
Journal Articles
Status:
Published
Year Published:
2013
Citation:
Angew Chem Int Ed Engl. 2013 Jan 28;52(5):1590-4. doi: 10.1002/anie.201207456. Epub 2012 Dec 20.
Homologous NRPS-like gene clusters mediate redundant small-molecule biosynthesis in Aspergillus flavus.
Forseth RR1, Amaike S, Schwenk D, Affeldt KJ, Hoffmeister D, Schroeder FC, Keller NP.
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