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Microfluidic approaches to malaria pathogenesis

Meher Antia, Thurston Herricks, Pradipsinh K. Rathod
2008 Cellular Microbiology  
Herricks, M. Antia and P.K. Rathod, in preparation).  ...  Recently, we have adapted a microfluidic technique previously used on uninfected RBCs to accurately measure the cell's surface area and volume (Herricks et al. unpubl. data; Fig. 2B) .  ... 
doi:10.1111/j.1462-5822.2008.01216.x pmid:18754851 pmcid:PMC3818003 fatcat:dfv6w6mklbgl3dmdhpb6wuf56y

Deformability limits ofPlasmodium falciparum-infected red blood cells

Thurston Herricks, Meher Antia, Pradipsinh K. Rathod
2009 Cellular Microbiology  
Splenic filtration of infected red blood cells (RBCs) may contribute to innate immunity and variable outcomes of malaria infections. We show that filterability of individual RBCs is well predicted by the minimum cylindrical diameter (MCD) which is calculated from a RBC's surface area and volume. The MCD describes the smallest diameter tube or smallest pore that a cell may fit through without increasing its surface area. A microfluidic device was developed to measure the MCD from thousands of
more » ... ividual infected RBCs (IRBCs) and uninfected RBCs (URBCs). Average MCD changes during the blood-stage cycle of Plasmodium falciparum were tracked for the cytoadherent strain ITG and the knobless strain Dd2. The MCD values for IRBCs and URBCs raise several new intriguing insights into how the spleen may remove IRBCs: some early-stage ring-IRBCs, and not just latestage schizont-IRBCs, may be highly susceptible to filtration. In addition, knobby parasites may limit surface area expansions and thus confer high MCDs on IRBCs. Finally, URBCs, in culture with IRBCs, show higher surface area loss which makes them more susceptible to filtration than naive URBCs. These findings raise important basic questions about the variable pathology of malaria infections and metabolic process that affect volume and surface area of IRBCs.
doi:10.1111/j.1462-5822.2009.01334.x pmid:19438513 pmcid:PMC2774476 fatcat:q6rwz3tobvg47dnfnhgnwd6lfi

Microfluidic Modeling of Cell−Cell Interactions in Malaria Pathogenesis

Meher Antia, Thurston Herricks, Pradipsinh K. Rathod
2007 PLoS Pathogens  
Citation: Antia M, Herricks T, Rathod PK (2007) Microfluidic modeling of cell-cell interactions in malaria pathogenesis. PLoS Pathog 3(7): e99.  ... 
doi:10.1371/journal.ppat.0030099 pmid:17658948 pmcid:PMC1924869 fatcat:3heq3qcfz5e77brzlyoscjsqha

ESCRT-III acts in scissioning new peroxisomes from the ER [article]

Fred D Mast, Thurston Herricks, Kathleen M Strehler, Leslie R Miller, Ramsey A Saleem, Richard A Rachubinski, John D Aitchison
2017 bioRxiv   pre-print
Dynamic control of peroxisome proliferation is integral to the peroxisome's many functions. A breakdown in the ability of cells to form peroxisomes is linked to many human health issues, including defense against infectious agents, cancer, aging, heart disease, obesity and diabetes, and forms the basis of a spectrum of peroxisomal genetic disorders that cause severe neuropathologies. The ER serves as a source for preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo
more » ... me biogenesis and to support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. Here we show that the evolutionarily ancient endosomal sorting complexes required for transport (ESCRT)-III are peroxisome biogenesis factors that function to cleave PPVs budding from the ER into the cytosol. Using comprehensive morphological and genetic assays of peroxisome formation and function we find that absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay we show that ESCRT-III proteins Vps20 and Snf7 are required to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and towards the cytosol, a finding that has important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.
doi:10.1101/147603 fatcat:3tr6sprrh5bopnzr6v2qy5kzka

One-cell Doubling Evaluation by Living Arrays of Yeast, ODELAY! [article]

Thurston Herricks, David J Dilworth, Fred D Mast, Song Li, Jennifer J Smith, Alexander V Ratushny, John D Aitchison
2016 bioRxiv   pre-print
Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single cell resolution
more » ... provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAY extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.
doi:10.1101/069724 fatcat:zfhss7tyrfcszhz73o6qxadare

ODELAM: Rapid Sequence-independent Detection of Drug Resistance in Mycobacterium tuberculosis Isolates

Thurston Herricks, Magdalena Donczew, David Sherman, John Aitchison
2021 Bio-protocol  
Copyright Herricks et al. This article is distributed under the terms of the Creative Commons Attribution License (CC BY 4.0). cite this article as: Herricks et al., (2021) .  ...  Thermometer (VWR, catalog number: 89095-640) Table 1 . 1 Volume recipes for the 7H9-GO Media Copyright Herricks et al.  ...  Please cite this article as: Herricks et al., (2021) . ODELAM: Rapid Sequence-independent Detection of Drug Resistance in Mycobacterium tuberculosis Isolates. Bio-protocol 11(10): e4027.  ... 
doi:10.21769/bioprotoc.4027 pmid:34150934 pmcid:PMC8187124 fatcat:jh6oofwka5dm3m6s7755vq6eju

ODELAY: A Large-scale Method for Multi-parameter Quantification of Yeast Growth

Thurston Herricks, Fred D. Mast, Song Li, John D. Aitchison
2017 Journal of Visualized Experiments  
Growth phenotypes of microorganisms are a strong indicator of their underlying genetic fitness and can be segregated into 3 growth regimes: lag-phase, log-phase, and stationary-phase. Each growth phase can reveal different aspects of fitness that are related to various environmental and genetic conditions. High-resolution and quantitative measurements of all 3 phases of growth are generally difficult to obtain. Here we present a detailed method to characterize all 3 growth phases on solid media
more » ... using an assay called One-cell Doubling Evaluation of Living Arrays of Yeast (ODELAY). ODELAY quantifies growth phenotypes of individual cells growing into colonies on solid media using time-lapse microscopy. This method can directly observe population heterogeneity with each growth parameter in genetically identical cells growing into colonies. This population heterogeneity offers a unique perspective for understanding genetic and epigenetic regulation, and responses to genetic and environmental perturbations. While the ODELAY method is demonstrated using yeast, it can be utilized on any colony forming microorganism that is visible by bright field microscopy.
doi:10.3791/55879 pmid:28715382 pmcid:PMC5608540 fatcat:7kk25qto2ncfpcgfwxg4ushmuu

ODELAM: Rapid sequence-independent detection of drug resistance in clinical isolates of Mycobacterium tuberculosis [article]

Thurston Herricks, Madalena Donczew, Fred Mast, Tige Rustad, Robert Morrison, Timothy R Sterling, David Sherman, John D. Aitchison
2020 bioRxiv   pre-print
org/10.1101 org/10. /2020 Agarose was prepared as described previously (Herricks et al. 2017) . Bulk agarose was prepared by dissolving 2 g of agarose in 150 g of 18 MΩ H2O.  ...  Originally designed for yeast, the adaptation offers improvements on phenotypic analysis and diagnostics for detecting and characterizing populations of drug resistant Mtb (Herricks et al. 2017 ).  ... 
doi:10.1101/2020.03.17.995480 fatcat:mqlaswserncnjilqnn4pcxy24y

Estimating physical splenic filtration ofPlasmodium falciparum-infected red blood cells in malaria patients

Thurston Herricks, Karl B. Seydel, Malcolm Molyneux, Terrie Taylor, Pradipsinh K. Rathod
2012 Cellular Microbiology  
The cultured schizonts have MCDs larger than 2.75 µm which is larger than the majority of uninfected RBCs (Herricks et al., 2009 ).  ...  Batch image analysis was performed using routines written in MATLAB R2010a (Mathworks) as described previously (Herricks et al., 2009 ).  ... 
doi:10.1111/cmi.12007 pmid:22892025 pmcid:PMC3501548 fatcat:ovdheaqhgbgbbjlbcyg5rserjy

ODELAM Rapid sequence-independent detection of drug resistance in isolates of Mycobacterium tuberculosis

Thurston Herricks, Magdalena Donczew, Fred D Mast, Tige Rustad, Robert Morrison, Timothy R Sterling, David R Sherman, John D Aitchison
2020 eLife  
A course grid 395 optimization routine was used if the geometric approximation failed (Herricks et al., 2017) .  ...  Each spot was imaged every 30 min for up to 120 hrs. 371 Analysis of the images was performed as described in Herricks et al., 2017 .  ... 
doi:10.7554/elife.56613 pmid:32401195 pmcid:PMC7263823 fatcat:nmjs45rvsvbf7kiplt5lphdska

One-Cell Doubling Evaluation by Living Arrays of Yeast, ODELAY!

Thurston Herricks, David J. Dilworth, Fred D. Mast, Song Li, Jennifer J. Smith, Alexander V. Ratushny, John D. Aitchison
2016 G3: Genes, Genomes, Genetics  
Cell growth is a complex phenotype widely used in systems biology to gauge the impact of genetic and environmental perturbations. Due to the magnitude of genome-wide studies, resolution is often sacrificed in favor of throughput, creating a demand for scalable, time-resolved, quantitative methods of growth assessment. We present ODELAY (One-cell Doubling Evaluation by Living Arrays of Yeast), an automated and scalable growth analysis platform. High measurement density and single-cell resolution
more » ... provide a powerful tool for large-scale multiparameter growth analysis based on the modeling of microcolony expansion on solid media. Pioneered in yeast but applicable to other colony forming organisms, ODELAY extracts the three key growth parameters (lag time, doubling time, and carrying capacity) that define microcolony expansion from single cells, simultaneously permitting the assessment of population heterogeneity. The utility of ODELAY is illustrated using yeast mutants, revealing a spectrum of phenotypes arising from single and combinatorial growth parameter perturbations.
doi:10.1534/g3.116.037044 pmid:27856698 pmcid:PMC5217116 fatcat:744gfilb25d4hhgc4rqobds7iu

Combining inferred regulatory and reconstructed metabolic networks enhances phenotype prediction in yeast [article]

Zhuo Wang, Samuel A Danziger, Benjamin D Heavner, Shuyi Ma, Jennifer J Smith, Song Li, Thurston Herricks, Evangelos Simeonidis, Nitin S Baliga, John D Aitchison, Nathan D Price
2016 bioRxiv   pre-print
Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced REgulation And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models
more » ... ith the PROM framework to create enhanced metabolic-regulatory network models. We used IDREAM to predict phenotypes and genetic interactions between transcription factors and genes encoding metabolic activities in the eukaryote, Saccharomyces cerevisiae. IDREAM models contain many fewer interactions than PROM and yet produce significantly more accurate growth predictions. IDREAM consistently outperformed PROM using any of three popular yeast metabolic models and across three experimental growth conditions. Importantly, IDREAM's enhanced accuracy makes it possible to identify subtle synthetic growth defects. With experimental validation, these novel genetic interactions involving the pyruvate dehydrogenase complex suggested a new role for fatty acid-responsive factor Oaf1 in regulating acetyl-CoA production in glucose grown cells.
doi:10.1101/087148 fatcat:dgknrzy2mrcwzb3q7mev2h7fqi

ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum

Fred D. Mast, Thurston Herricks, Kathleen M. Strehler, Leslie R. Miller, Ramsey A. Saleem, Richard A. Rachubinski, John D. Aitchison
2018 Journal of Cell Biology  
The YPB-oleate medium was then cast into molds and allowed to cool as described previously (Herricks et al., 2017a) .  ...  Sensitive, high-density, and multiparametric analysis of cell growth was performed as described previously (Herricks et al., 2017a,b) .  ... 
doi:10.1083/jcb.201706044 pmid:29588378 fatcat:lgoerrlpqveitcmfolsdirczn4

A microfluidic system to study cytoadhesion of Plasmodium falciparum infected erythrocytes to primary brain microvascularendothelial cells

Thurston Herricks, Karl B. Seydel, George Turner, Malcolm Molyneux, Robert Heyderman, Terrie Taylor, Pradipsinh K. Rathod.
2011 Lab on a Chip  
The cellular events leading to severe and complicated malaria in some Plasmodium falciparum infections are poorly understood. Additional tools are required to better understand the pathogenesis of this disease. In this technical report, we describe a microfluidic culture system and image processing algorithms that were developed to observe cytoadhesion interactions of P. falciparum parasitized erythrocytes rolling on primary brain microvascularendothelial cells. We isolated and cultured human
more » ... imary vascular endothelial cells in a closed loop microfluidic culture system where a peristaltic pump and media reservoirs were integrated onto a microscope stage insert. We developed image processing methods to enhance contrast of rolling parasitized erythrocytes on endothelial cells and to estimate the local wall shear stress. The velocity of parasitized erythrocytes rolling on primary brain microvascularendothelial cells was then measured under physiologically relevant wall shear stresses. Finally, we deployed this method successfully at a field site in Blantyre, Malawi. The method is a promising new tool for the investigation of the pathogenesis of severe malaria.
doi:10.1039/c1lc20131j pmid:21743938 pmcid:PMC3809019 fatcat:ifp6setl3rbf5ph5chk6rglbtm

Clonal Variants of Plasmodium falciparum Exhibit a Narrow Range of Rolling Velocities to Host Receptor CD36 under Dynamic Flow Conditions

Thurston Herricks, Marion Avril, Joel Janes, Joseph D. Smith, Pradipsinh K. Rathod
2013 Eukaryotic Cell  
Cytoadhesion of Plasmodium falciparum parasitized red blood cells (pRBCs) has been implicated in the virulence of malaria infection. Cytoadhesive interactions are mediated by the protein family of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). The PfEMP1 family is under strong antibody and binding selection, resulting in extensive sequence and size variation of the extracellular domains. Here, we investigated cytoadhesion of pRBCs to CD36, a common receptor of P. falciparum
more » ... isolates, under dynamic flow conditions. Isogeneic parasites, predominantly expressing single PfEMP1 variants, were evaluated for binding to recombinant CD36 under dynamic flow conditions using microfluidic devices. We tested if PfEMP1 size (number of extracellular domains) or sequence variation affected the pRBC-CD36 interaction. Our analysis showed that clonal parasite variants varied ∼5-fold in CD36 rolling velocity despite extensive PfEMP1 sequence polymorphism. In addition, adherent pRBCs exhibited a characteristic hysteresis in rolling velocity at microvascular flow rates, which was accompanied by changes in pRBC shape and may represent important adaptations that favor stable binding.
doi:10.1128/ec.00148-13 pmid:24014767 pmcid:PMC3837943 fatcat:lxfqe3i5jjh6vlfz2jr2chdq3a
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