A5088801360- Fermentation and Sensory Analysis
- Yeasts and Rust Fungi Studies
- Malaria Research and Control
- Biofuel production and bioconversion
- Fungal and yeast genetics research
- Microbial Metabolic Engineering and Bioproduction
- Horticultural and Viticultural Research
- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Synthesis and bioactivity of alkaloids
- Mosquito-borne diseases and control
- Neuropeptides and Animal Physiology
- Invertebrate Immune Response Mechanisms
- Neonatal Health and Biochemistry
- Liver Disease and Transplantation
- HIV Research and Treatment
- Toxoplasma gondii Research Studies
- Computational Drug Discovery Methods
- Insect symbiosis and bacterial influences
- Plant Pathogens and Resistance
- Heat shock proteins research
- Protist diversity and phylogeny
- Protein Degradation and Inhibitors
- Heme Oxygenase-1 and Carbon Monoxide
- Evolution and Genetic Dynamics
Duke University Hospital
2018-2024
Duke Medical Center
2018-2024
Duke University
2018-2024
University of Wisconsin–Madison
2014-2021
Great Lakes Bioenergy Research Center
2014-2021
Energy Center of Wisconsin
2015-2020
Indiana University School of Medicine
2019
Durham Technical Community College
2019
Abstract Reticulate evolution can be a major driver of diversification into new niches, especially in disturbed habitats and at the edges ranges. Industrial fermentation strains yeast provide window these processes, but progress has been hampered by limited understanding natural diversity distribution S accharomyces species populations. For example, lager beer is brewed with pastorianus , an alloploid hybrid . cerevisiae eubayanus only recently discovered P atagonia, A rgentina. Here, we...
Lager-style beers constitute the vast majority of beer market, and yet, genetic origin yeast strains that brew them has been shrouded in mystery controversy. Unlike ale-style beers, which are generally brewed with Saccharomyces cerevisiae, lagers at colder temperatures allopolyploid hybrids eubayanus x S. cerevisiae. Since discovery 2011, additional have isolated from South America, North Australasia, Asia, but only interspecies Europe. Here, using genome sequence data, we examine...
Compared to its status as an experimental model system and importance industry, the ecology genetic diversity of genus Saccharomyces has received less attention. To investigate systematically biogeography, community members habitat these important yeasts, we isolated identified nearly 600 yeast strains using sugar-rich enrichment protocols. Isolates were highly diverse contained representatives more than 80 species from over 30 genera, including eight novel that describe here: Kwoniella...
Exploring the ability of organisms to locally adapt is critical for determining outcome rapid climate changes, yet few studies have addressed this question in microorganisms. We investigated role a heterogeneous on adaptation North American populations wild yeast Saccharomyces paradoxus. found abundant among-strain variation fitness components across range temperatures, but was only partially explained by climatic distribution area. Most divergence genetically distinct groups, distributed...
Lignocellulosic biomass is a common resource across the globe, and its fermentation offers promising option for generating renewable liquid transportation fuels. The deconstruction of lignocellulosic releases sugars that can be fermented by microbes, but these processes also produce inhibitors, such as aromatic acids aldehydes. Several research projects have investigated baker's yeast Saccharomyces cerevisiae. Most taken synthetic biological approaches or explored naturally occurring...
ABSTRACT Budding yeasts are distributed across a wide range of habitats, including as human commensals. However, under some conditions, these commensals can cause superficial, invasive, and even lethal infections. Despite their importance to health, little is known about the ecology opportunistic pathogens, aside from associations with mammals clinical environments. During survey approximately 1000 non-clinical samples United States America, we isolated 54 strains budding yeast species...
Within the liver a single Plasmodium parasite transforms into thousands of blood-infective forms to cause malaria. Here, we use RNA-sequencing identify host genes that are upregulated upon berghei infection hepatocytes with hypothesis pathways hijacked benefit development. We found expression aquaporin-3 (AQP3), water and glycerol channel, is significantly induced in Plasmodium-infected compared uninfected cells. This aquaglyceroporin localizes parasitophorous vacuole membrane, compartmental...
The wild, cold-adapted parent of hybrid lager-brewing yeasts, Saccharomyces eubayanus, has a complex and understudied natural history. exploration this diversity can be used both to develop new brewing applications enlighten our understanding the dynamics yeast evolution in wild. Here, we integrate whole genome sequence phenotypic data 200 S. eubayanus strains, largest collection known date. multilayered population structure, consisting two major populations that are further structured into...
Plasmodium vivax infects hepatocytes to form schizonts that cause blood infection, or dormant hypnozoites can persist for months in the liver before leading relapsing infections. The molecular processes drive P. schizont and hypnozoite survival remain largely unknown, but they likely involve a rich network of host-pathogen interactions, including those occurring at host-parasite interface, parasitophorous vacuole membrane (PVM). Using recently developed liver-stage model system we...
The antihistamine clemastine inhibits multiple stages of the Plasmodium parasite that causes malaria, but molecular targets responsible for its inhibition were unknown. Here, we applied parallel chemoproteomic platforms to discover mechanism action and identify binds falciparum TCP-1 ring complex or chaperonin containing (TRiC/CCT), an essential heterooligomeric required de novo cytoskeletal protein folding. Clemastine destabilized all eight P. TRiC subunits based on thermal proteome...
The apicomplexan parasites Plasmodium spp. are the causative agents of malaria, a disease that poses significant global health burden. initiate infection human host by transforming and replicating within hepatocytes. This liver stage (LS) is poorly understood compared to other life stages, which has hindered our ability target these for prevention. We conducted an extensive transcriptome sequencing (RNA-Seq) analysis throughout berghei LS, covering as early 2 h postinfection (hpi) extending...
Abstract The development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one world’s most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged attractive targets for malaria chemotherapy. We describe a single-step biochemical assay Plasmodium synthetases overcomes critical limitations existing technologies enables quantitative inhibitor profiling...
Abstract Yeasts have broad importance as industrially and clinically relevant microbes powerful models for fundamental research, but we are only beginning to understand the roles yeasts play in natural ecosystems. Yeast ecology is often more difficult study compared other, abundant microbes, growing collections of yeast isolates shed light on ecological questions. Here, used environmental sampling isolation assemble a dataset 1962 collected from throughout contiguous United States America...
We describe a tandem reaction leading to tricyclic pyrrolo[1,2-<italic>a</italic>]quinolin-5-ones with unique selectivity against the liver stage of malaria parasite.
Plasmodium is a genus of apicomplexan parasites which replicate in the liver before causing malaria. vivax can also persist as dormant hypnozoites and cause clinical relapse upon activation, but molecular mechanisms leading to activation have yet be discovered. In this study, we use high-resolution microscopy characterize temporal changes P. stage tubovesicular network (TVN), parasitophorous vacuole membrane (PVM)-derived within host cytosol. We observe extended clusters, tubules,...
Abstract An in silico screen of 350 000 commercially available compounds was conducted with an unbiased approach to identify potential malaria inhibitors that bind the Plasmodium falciparum protein kinase 5 ( Pf PK5) ATP‐binding site. P f PK5 is a cyclin‐dependent kinase‐like high sequence similarity human 2 Hs CDK2), but its precise role cell‐cycle regulation remains unclear. After two‐dimensional fingerprinting top scoring compounds, 182 candidates were prioritized for biochemical testing...
Abstract As traditional small‐molecule drug discovery programs focus on a relatively narrow range of chemical space, most human proteins are viewed as unreachable targets. Consequently, there is strong interest in expanding the space beyond small molecules. Here, strategy for preparation broad natural‐product‐like macrocyclic library by using tandem allylic oxidation/oxa‐conjugate addition and macrocyclization reactions reported. Cheminformatic analyses demonstrate that this...
Budding yeasts are distributed across a wide range of habitats, including as human commensals. However, under some conditions, these commensals can cause superficial, invasive, and even lethal infections. Despite their importance to health, little is known about the ecology opportunistic pathogens, aside from associations with mammals clinical environments. During survey approximately 1000 non-clinical samples United States America, we isolated 54 strains budding yeast species considered...
Abstract Hybridization is recognized as a powerful mechanism of speciation and driving force in generating biodiversity. However, only few multicellular species, limited to handful plants animals, have been shown fulfill all the criteria homoploid hybrid speciation. This lack evidence could lead misconception that by hybridization has role eukaryotes, particularly single-celled organisms. Laboratory experiments revealed fungi such budding yeasts can rapidly develop reproductive isolation...
Abstract S. eubayanus , the wild, cold-tolerant parent of hybrid lager-brewing yeasts, has a complex and understudied natural history. The exploration this diversity can be used both to develop new brewing applications enlighten our understanding dynamics yeast evolution in wild. Here, we integrate whole genome sequence phenotypic data 200 strains, largest collection date. multilayered population structure, consisting two major populations that are further structured into six subpopulations....
ABSTRACT The apicomplexans Toxoplasma gondii and Plasmodium are intracellular parasites that reside within a host-derived compartment termed the parasitophorous vacuole (PV). During infection, must acquire critical host resources transport them across their PV for development. However, mechanism by which trafficked to remains uncertain. Here, we investigated ADP ribosylation factors (Arfs), class of proteins involved in vesicular trafficking may be exploited T. berghei nutrient acquisition....