第30届真菌遗传会议的未来科学家

Editors ofFungal Biology and Biotechnologyrecently attended the 30th Fungal Genetics Conference in Pacific Grove, CA, USA. We invited young scientists who presented excellent posters at the conference to tell us more about their research. In this blog, we hear from Hans Mattila, Itai Brand-Thomas, Ken Miyazawa, Emmanuelle LeBlanc, and Norman Paege about their work.

Wood decomposition under hypoxia: Towards sustainable bioethanol production – Hans Mattila

基本菌fungi that grow on tree trunks and pieces of dead wood are a familiar sight in our forests. However, the eye-catching fruiting body of a wood decomposer is only part of the organism. Wood decomposition itself is actually orchestrated by its hypha that elongates beneath the bark and even penetrates the dead wood.

生长在树干上

As a mycologist, I wondered how wood decomposition can take place inside waterlogged pieces of wood where the hyphae must encounter temporal or regional oxygen depletion. This led us thinking that these organisms could be capable of fermenting ethanol while decomposing untreated wood-based materials under hypoxia.

Our research presents new potential regulative factors within the well-studied ethanol fermentation and primary metabolism pathways.

I started my Ph.D. project to test this hypothesis by screening基本菌Polyporalesfungi for their capability for simultaneous saccharification and fermentation (SSF). A white-rot isolatePhlebia radiata 79,outperformed other candidates by bioconverting various unpretreated lignocellulose materials under oxygen-limited conditions.P. radiata能够分解软木,硬木,再生木材废物以及大麦和小麦稻草(Mattila等。2017,2018).

We extended our research to better comprehend how SSF related pathways are regulated inP. radiata. Thus we extracted and sequenced RNA from various culture conditions and combined the information with promoter regions analysis.

Decomposing wood products

First, we noticed thatP. radiatareacts differently to hypoxia compared to well-studiedAscomycotaspecies. In fact, the hypoxic response ofP. radiata类似于一个基本菌speciesCryptococcus neoformans. Our research presents new potential regulative factors within the well-studied ethanol fermentation and primary metabolism pathways.

其次,我们了解到缺氧改变了分泌木材分解(Cazy)酶的特征。根据我们的结果,缺氧似乎是Cazy基因的同样重要的调节剂,而生长底物的组成也是如此(Kuuskeri等。2016).

Altogether we believe our research moves us one step closer towards sustainable 2ndgeneration bioethanol production.

In conclusion, our research tries to shed light on the regulative aspects behind SSF. This has aided our applicative project which aims to a novel type of bioethanol production method. We try to comprehend the gene regulation of a wood decomposing organism that has the capability to use a versatile selection of solid substrates. Altogether we believe our research moves us one step closer towards sustainable 2ndgeneration bioethanol production.

Hans is Doctoral Student in the Department of Microbiology at the University of Helsinki, Finland. He started his Ph.D. project to test the hypothesis that Basidiomycota fungi could be capable of fermenting ethanol while decomposing untreated wood-based materials under hypoxia. The research started by screening Basidiomycota Polyporales fungi for their capability for simultaneous saccharification and fermentation (SSF), and then it was extended to better comprehend how SSF related pathways are regulated in P. radiata.

Leveraging metatranscriptomics and synthetic biology to enhance our understanding of the biomass-degrading machinery of anaerobic fungi – Itai Brand-Thomas

I am intrigued by how microbes interact with their host environments and the effects of these interactions on human and animal health. I am excited about the opportunity to conduct interdisciplinary research that utilizes both cultivation independent omics techniques and wet-lab microbiology to learn about a phylogenetic group that is poorly understood, despite its importance to host function and health.

Prior to the mid-1970s it was assumed that fungi required oxygen for survival and growth…

在1970年代中期之前,假定真菌需要氧气才能生存和生长,只有在此期间,厌氧真菌才被描述为这样。从那时起,已经确定瘤胃的厌氧真菌代表了一些最多产的生物量降解剂,而最近的基因组研究表明,厌氧瘤胃真菌具有富含碳水化合物活性酶的基因组(CAZYMES)。瘤胃的正确功能依赖于古细菌,细菌,真菌,原生动物和病毒的相互作用。

尽管使用耕作和培养独立的技术对原核生物瘤胃的种群进行了充分的研究,但有关瘤胃真菌种群的研究数量仍然很低。缺乏对这个重要功能群体的生物学知识,导致瘤胃生态系统的不完整情况,并导致模型中的不准确性,这些模型预测了反刍动物饮食的变化如何影响瘤胃功能和健康。

通过研究瘤胃真菌及其酶,可以增强我们对瘤胃微生物群落协同性质并改善当前模型的协同性的理解。这将有助于发展高级策略,以改善瘤胃功能和宿主动物的健康,同时减少肠发酵的环境影响,即减少有效的温室气甲烷的生产和释放。

Furthermore, I anticipate that previously uncharacterized CAZymes from anaerobic fungi might complement their bacterial counterparts, representing the missing link to develop more efficient enzyme cocktails for industrial biomass degradation and the production of novel bioproducts.

…来自厌氧菌真菌的未表征可能会补充其细菌的对应物,代表缺失的链接,以开发更有效的酶鸡尾酒来用于工业生物量降解和生产新型生物生物生物生物生物生物生物生物生物。

我自己的研究,我一直利用metatranscriptomics to study the anaerobic fungi that colonize and degrade recalcitrant plant material during rumen-incubation. I have been able to assemble thousands of CAZyme transcripts from the population of anaerobic rumen population, and subsequent sequence analysis has revealed that these fungal CAZymes have a rather low overall sequence similarity to currently known, primarily bacterial CAZymes. The CAZymes identified in the course of this work is expected to significantly expand the diversity within the CAZyme universe.

I am currently in the process of biochemically characterizing and obtaining crystal structures of some of the newly identified CAZymes to verify their predicted activity and to obtain a better understanding of the molecular mechanisms by which these fungal CAZymes facilitate the degradation of plant biomass under anaerobic conditions.

…find a topic that you are passionate about and use that excitement to fuel your research.

The advice I would give to young scientists starting out in research is: find a topic that you are passionate about and use that excitement to fuel your research. Don’t be intimidated by large amounts of data or a technique you are unfamiliar with; give it a shot, ask questions along the way, and learn from your mistakes. Make sure to find time for activities outside of research. This will allow you to approach your studies with a different perspective and allow you to take a mental break and re-energize.

(Acknowledgements: I was able to attend to the Fungal Genetics Conference thanks to funding from the Alumni Foundation of Amherst College).

Itai is a first-year graduate student in the Systems Microbiology & Natural Products Laboratory at the University of California in Davis (USA). Her thesis project centers on anaerobic fungi that inhabit the rumen of the cow and the enzymes secreted by this significantly understudied group of microorganisms.

使用丝状真菌的发酵行业的创新 - Ken Miyazawa

Aspergillus nidulans
credit:Plasmidmap/222fjb - wikipedia

细胞壁Aspergillusspecies is mainly composed of polysaccharides including α-1,3-glucan. We previously reported that α-1,3-glucan has a role for hyphal aggregation inAspergillus nidulanswhich possesses two α-1,3-glucan synthase genes (agsAandagsB).

在这里,我们构建了过表达的压力agsA(agsAOE) oragsB(agsBOE). The degree of hyphal aggregation was different between the overexpressing strains; tightly aggregated in theagsBOE,而在agsAOE.

Size-exclusion-chromatography analysis of α-1,3-glucan revealed that the molecular mass of α-1,3-glucan from theagsAOEwas four times larger than that from theagsBOE.

In addition, fluorophore-labeling of hyphal polysaccharides suggested that spatial localization of α-1,3-glucan in the cell wall was different between the overexpressing strains; outer layer in theagsBOE, whereas in the inner layer in theagsAOE. Taken together, hyphal pellet formation depends on the molecular mass and localization of α-1,3-glucan as well as the amount of α-1,3-glucan in the cell wall ofA.nidulans.

我们的研究将为使用丝状真菌的发酵行业提供潜在的创新。

由于我们先前报道了工业真菌的α-1,3-葡聚糖缺陷突变体Aspergillusoryzae分泌蛋白质产生的两次比野生型菌株增加了两次,了解菌丝聚集的机制可能有助于提高发酵生产率。我们的研究将为使用丝状真菌的发酵行业提供潜在的创新。

Ken是日本Tohoku University的应用微生物学实验室(Keietsu教授)实验室的博士学位。他的研究项目是开发新技术,通过分析细胞壁多糖的功能来提高真菌行业的发酵生产率。

Development of fungal-selective molecules and strategies to target Hsp90 – Emmanuelle LeBlanc

结构的一半酵母
credit - Wikipedia

Fungi infect over a billion people worldwide, posing a great burden on human health. Invasive fungal infections kill an estimated 1.5 million people annually. These numbers continue to rise with the increase in immunocompromised populations and high-risk individuals. The three most prevalent agents of invasive fungal disease areCandida albicans,Cryptococcus neoformansand曲霉菌. New therapeutic strategies are imperative as the three major classes of antifungals are hampered by host toxicity, the emergence of drug resistance, and a narrow activity spectrum.

Selective targeting of stress responses in fungal pathogens provides a promising therapeutic strategy to mitigate drug resistance and combat invasive mycoses. The molecular chaperone Hsp90 has been extensively validated as an essential regulator of virulence traits and antifungal resistance inCandidaspecies. However, toxicity of the current Hsp90 inhibitors, that inhibit the host chaperone, impedes their use as antifungal treatments.

我的项目旨在评估靶向真菌病原体中HSP90的治疗潜力。我与一支出色的国际团队紧密合作,包括来自结构基因组学联盟的专家,以及波士顿大学分子发现中心。通过结构活性关系,我们一起在天然产物HSP90抑制剂的类似物中优化了真菌选择性。这种跨学科的合作使我们能够结合结构,化学,生化和遗传方法,以设计合成化合物,并具有> 25倍的真菌选择性C. albicansandC. neoformans.

My goal is to uncover new biology and provide important insights supporting the feasibility of targeting Hsp90 and its regulatory circuit to treat deadly fungal infections.

In parallel, I aim to identify fungal-specific Hsp90 circuitry that governs stress responses and virulence inC. neoformans. My goal is to uncover new biology and provide important insights supporting the feasibility of targeting Hsp90 and its regulatory circuit to treat deadly fungal infections.

Emmanuelle是多伦多大学分子遗传学系Leah Cowen博士实验室的硕士学生。她还是一名铁人三项运动员,也是一位有抱负的临床医生。

When two fungi quarrel the human profits – Norman Paege

Cocultivation of A. niger (black, left side) and A. giganteus (grey, right side) on an agar plate.
Cocultivation of A. niger (black, left side) and A. giganteus (grey, right side) on an agar plate.

I am in the sixth year of my doctoral degree studies at the TU Berlin with two short interruptions due to paternity leave.

My research focus is on the mode of action of the antifungal protein AFP secreted from the filamentous fungus曲曲霉giganteus. It is of great importance to develop new antifungal strategies, particularly due to a world-wide increase in problems with fungal resistance and infections, which has resulted in damage to agriculture and crop loss, and serious impact on human health.

在我们的研究项目中,我们首先试图找到确定AFP灵敏度的元素。我们的重点是真菌质膜和真菌物种之间的差异。我们发现,小变化很重要,对法新社的敏感性产生了很大影响。

Secondly, we are working on understanding the role of AFP plays for its host. We have found more than 80 orthologues of this peptide spread throughout the fungal kingdom. Luckily, one, the AnAFP, is produced byA. niger. With the use of our transcriptome database including 155 growth conditions, we concluded that AnAFP is involved in several metabolic processes active during carbon starvation or autophagy.

…it is crucial to define your own topic right at the beginning of your doctoral research, and try to be consistent in following it through.

在我的研究经历我学会了——而这s is the advice I’d like to share with young scientists starting out in research – that it is crucial to define your own topic right at the beginning of your doctoral research, and try to be consistent in following it through.

此外,我发现的另一项建议很重要:如果您想使用一种新方法,请尝试与实验室建立合作。这将确保支持和更好的进步。

Norman is Doctoral Student in the Department for Applied and Molecular Microbiology (AMM) at TU Berlin, Germany. His research focuses on studying the mode of action of the antifungal protein AFP secreted from the filamentous fungus Aspergillus giganteus, and his research interests aim at developing new antifungal strategies against increasingly more resistant fungal infections.

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