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Tag: Jessica Kissinger

Noncoding RNAs in Apicomplexan Parasites: An Update

Illustration of Long Noncoding RNA (lncRNA) Functions in Apicomplexan Parasites.

Recent breakthroughs in high-throughput technologies, transcriptomics, and advances in our understanding of gene regulatory networks have enhanced our perspective on the complex interplay between parasite and host. Noncoding RNA molecules have been implicated in critical roles covering a broad range of biological processes in the Apicomplexa. Processes that are affected range from parasite development to host–parasite interactions and include interactions with epigenetic machinery and other regulatory factors. Here we review recent progress involving noncoding RNAs and their functions in the Apicomplexa, with a focus on three parasites: PlasmodiumToxoplasma, and Cryptosporidium. We discuss the limitations and challenges of current methods applied to apicomplexan noncoding RNA study and discuss future directions in this exciting field.

 

 

 

Yiran Li, Rodrigo P. Baptista, Jessica C. Kissinger. Trends Parasitol. 2020 Aug 19;S1471-4922(20)30189-6. https://doi.org/10.1016/j.pt.2020.07.006

Update on Cryptosporidium spp.: highlights from the Seventh International Giardia and Cryptosporidium Conference

While cryptosporidiosis is recognized as being among the most common causes of human parasitic diarrhea in the world, there is currently limited knowledge on Cryptosporidium infection mechanisms, incomplete codification of diagnostic methods, and a need for additional therapeutic options. In response, the Seventh International Giardia and Cryptosporidium Conference (IGCC 2019) was hosted from 23 to 26 June 2019, at the Rouen Normandy University, France. This trusted event brought together an international delegation of researchers to synthesize recent advances and identify key research questions and knowledge gaps. The program of the interdisciplinary conference included all aspects of host-parasite relationships from basic research to applications to human and veterinary medicine, and environmental issues associated with waterborne parasites and their epidemiological consequences. In relation to Cryptosporidium and cryptosporidiosis, the primary research areas for which novel findings and the most impressive communications were presented and discussed included: Cryptosporidium in environmental waters, seafood, and fresh produce; Animal epidemiology; Human cryptosporidiosis and epidemiology; Genomes and genomic evolution encompassing: Comparative genomics of Cryptosporidium spp., Genomic insights into biology, Acquiring and utilizing genome sequences, Genetic manipulation; Host-parasite interaction (immunology, microbiome); and Diagnosis and treatment. High quality presentations discussed at the conference reflected decisive progress and identified new opportunities that will engage investigators and funding agencies to spur future research in a “one health” approach to improve basic knowledge and the clinical and public health management of zoonotic cryptosporidiosis.

Giovanni Widmer, David Carmena, Martin Kváč, Rachel M. Chalmers, Jessica C. Kissinger, Lihua Xiao, Adam Sateriale, Boris Striepen, Fabrice Laurent, Sonia Lacroix-Lamandé, Gilles Gargala and Loïc Favennec. Parasite. 2020;27:14. doi: 10.1051/parasite/2020011.

Sharing the Knowledge: NIH Award Supports Expanded Genomics Data Resource

By: Alan Flurry

A team led by scientists at the University of Pennsylvania and University of Georgia provides thousands of researchers around the world with access to the Eukaryotic Pathogen Genomics Database (EuPathDB.org), a collection of resources for analyzing large-scale datasets associated with microbial pathogens. These include the parasites responsible for malaria, sleeping sickness, and toxoplasmosis; the fungi responsible for thrush, aspergillosis and Valley Fever; and many other important diseases. In parallel, a team led by investigators at the University of Notre Dame has been responsible for similar resources covering invertebrate vectors of disease (VectorBase.org), including the mosquitoes transmitting malaria, Zika, and yellow fever, the ticks responsible for Lyme disease and Rocky Mountain Spotted Fever, and others.

To ensure that this important work continues, the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, has awarded a new contract to integrate these resources, worth up to $7.2 million in 2019-2020. The five‐year award for this project, rebranded as VEuPathDB.org (The Eukaryotic Pathogen, Host & Vector Genomics Resource) could total as much as $38.4 million if all associated options are exercised.

The patterns revealed by such “Big Data” provide insight into important diseases, permit the development of diagnostic methods, and define drug and vaccine targets. But to be useful, these immense datasets must be sensibly organized and made conveniently accessible to the researchers worldwide. The integrated VEuPathDB database hosts data on thousands of genomes, representing hundreds of species, along with extensive information on isolate provenance, gene function and the like.

The award is based at Penn, and directed by David S Roos, E Otis Kendall Professor of Biology in the School of Arts & Sciences. Key subcontracts include the University of Georgia (Joint PI Jessica C. Kissinger, Distinguished Professor of Genetics and Bioinformatics in the Franklin College of Arts and Sciences and the Center for Tropical and Emerging Global Diseases), University of Notre Dame (Joint PI Mary Ann McDowell, Associate Professor of Biological Sciences at the Eck Institute for Global Health).  Additional co-investigators include Professors Christian Stoeckert of Penn’s Perelman School of Medicine, Mark Caddick of the University of Liverpool, George K Christophides of Imperial College London, and Paul Flicek, Associate Director of the EMBL-EBI (European Bioinformatics Institute).

“It is wonderful to see the continued investment by NIH, the Wellcome Trust and others in resources that make performing much needed global research on infectious diseases both easier and better,” Kissinger said. “Datasets are larger and more complex than ever due to significant advances in technology. These breakthroughs create challenges for making the resulting data truly accessible and usable by the average researcher.  We strive to remove barriers, integrate diverse data and accelerate the speed with which new hypotheses can be generated and ideas tested both in silico and in the lab.”

“A critical aspect of this now joint program will be its accessibility throughout the world, empowering any infectious disease investigator to interrogate these highly complex databases in comprehensible and productive ways,” said Dan Colley, UGA professor of microbiology and member of the CTEGD who has conducted extensive research on n schistosomiasis in western Kenya. “These databases have led, and the merged data base will lead, to the design of new drugs and studies on how to better control and eliminate these major public health challenges, such as malaria, toxoplasmosis, yellow fever, eastern equine encephalitis and Lyme disease.”

“Since its conception, corresponding with the release of the first parasite genomes, EuPathDB has been a transformative tool in our search for a better understanding of human disease and parasite biology,” said Stephen Hadjuk, Professor Emeritus of biochemistry & molecular biology at UGA whose lab investigates trypanosomes, the causative agent of an human African sleeping sickness. “Today, it’s difficult to imagine any serious research on parasites and host pathology that doesn’t rely, at least to some extent, on EuPathDB. The decision to incorporate the vectors database into the eukaryotic pathogens database was brilliant, and makes this is an exciting new chapter in the EuPathDB story.”

“Innumerable investigators, including my own laboratory, rely on daily access to the high quality genomic and functional datasets made available by the VEuPathDB Project,” says Keith Gull, Professor of Molecular Microbiology at Oxford University.  “Sustainable support for such resources is imperative if we are to capitalize on the promise of modern technologies for scientific discovery and translational application.”  Joe Heitman, James B Duke Professor / Chair of Molecular Genetics & Microbiology at Duke University agrees: “Inclusion of fungal pathogens under the BRC umbrella has greatly enhanced our ability to study important human mycoses.  Cross-species comparisons provide insights into the biology and pathogenesis of these fascinating organisms, which can be deadly – but can also serve as workhorses for valuable biotechnology development.”

Originally published at https://www.franklin.uga.edu/news/stories/2019/sharing-knowledge-nih-award-supports-expanded-genomics-data-resource

Clinically silent relapsing malaria may still pose a threat

The immune system can control a relapsing form of malaria enough to avoid clinical signs of disease, but it doesn’t eliminate transmissible parasites from the body that may still be infectious to mosquitoes. That’s the conclusion of a study on a nonhuman primate model of Plasmodium vivax infection, which has implications relevant to malaria elimination strategies.

Keep reading about the MaPHIC study at Technology.org

Accessing Cryptosporidium Omic and Isolate Data via CryptoDB.org

Cryptosporidium has historically been a difficult organism to work with, and molecular genomic data for this important pathogen have typically lagged behind other prominent protist pathogens. CryptoDB ( http://cryptodb.org/ ) was launched in 2004 following the appearance of draft genome sequences for both C. parvum and C. hominis. CryptoDB merged with the EuPathDB Bioinformatics Resource Center family of databases ( https://eupathdb.org ) and has been maintained and updated regularly since its establishment. These resources are freely available, are web-based, and permit users to analyze their own sequence data in the context of reference genome sequences in our user workspaces. Advances in technology have greatly facilitated Cryptosporidium research in the last several years greatly enhancing and extending the data and types of data available for this genus. Currently, 13 genome sequences are available for 9 species of Cryptosporidium as well as the distantly related Gregarina niphandrodes and two free-living alveolate outgroups of the Apicomplexa, Chromera velia and Vitrella brassicaformis. Recent years have seen several new genome sequences for both existing and new Cryptosporidium species as well as transcriptomics, proteomics, SNP, and isolate population surveys. This chapter introduces the extensive data mining and visualization capabilities of the EuPathDB software platform and introduces the data types and tools that are currently available for Cryptosporidium. Key features are demonstrated with Cryptosporidium-relevant examples and explanations.

Warrenfeltz S, Kissinger JC, EuPathDB Team. Methods Mol Biol. 2020;2052:139-192. doi: 10.1007/978-1-4939-9748-0_10.

A Genetically Tractable, Natural Mouse Model of Cryptosporidiosis Offers Insights into Host Protective Immunity

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here, we derive an in vivo model of Cryptosporidium infection in immunocompetent C57BL/6 mice by isolating parasites from naturally infected wild mice. Similar to human cryptosporidiosis, this infection causes intestinal pathology, and interferon-γ controls early infection while T cells are critical for clearance. Importantly, mice that controlled a live infection were resistant to secondary challenge and vaccination with attenuated parasites provided protection equal to live infection. Both parasite and host are genetically tractable and this in vivo model will facilitate mechanistic investigation and rational vaccine design.

Adam Sateriale, Jan Šlapeta, Rodrigo Baptista, Julie B. Engiles, Jodi A. Gullicksrud, Gillian T. Herbert, Carrie F. Brooks, Emily M. Kugler, Jessica C. Kissinger, Christopher A. Hunter, Boris Striepen. Cell Host Microbe. 2019 Jun 18. pii: S1931-3128 (19) 30251-3. doi: 10.1016/j.chom.2019.05.006.

Distinct amino acid and lipid perturbations characterize acute versus chronic malaria

Chronic malaria is a major public health problem and significant challenge for disease eradication efforts. Despite its importance, the biological factors underpinning chronic malaria are not fully understood. Recent studies have shown that host metabolic state can influence malaria pathogenesis and transmission, but its role in chronicity is not known. Here, with the goal of identifying distinct modifications in the metabolite profiles of acute versus chronic malaria, metabolomics was performed on plasma from Plasmodium-infected humans and nonhuman primates with a range of parasitemias and clinical signs. In rhesus macaques infected with Plasmodium coatneyi, significant alterations in amines, carnitines, and lipids were detected during a high parasitemic acute phase and many of these reverted to baseline levels once a low parasitemic chronic phase was established. Plasmodium gene expression, studied in parallel in the macaques, revealed transcriptional changes in amine, fatty acid, lipid and energy metabolism genes, as well as variant antigen genes. Furthermore, a common set of amines, carnitines, and lipids distinguished acute from chronic malaria in plasma from human Plasmodium falciparum cases. In summary, distinct host-parasite metabolic environments have been uncovered that characterize acute versus chronic malaria, providing insights into the underlying host-parasite biology of malaria disease progression.

Regina Joice Cordy, Rapatbhorn Patrapuvich, Loukia N. Lili, Monica Cabrera-Mora, Jung-Ting Chien, Gregory K. Tharp, Manoj Khadka, Esmeralda V.S. Meyer, Stacey A. Lapp, Chester J. Joyner, AnaPatricia Garcia, Sophia Banton, ViLinh Tran, Viravarn Luvira, Siriwan Rungin, Teerawat Saeseu, Nattawan Rachaphaew, Suman B. Pakala, Jeremy D. DeBarry, MaHPIC Consortium, Jessica C. Kissinger, Eric A. Ortlund, Steven E. Bosinger, John W. Barnwell, Dean P. Jones, Karan Uppal, Shuzhao Li, Jetsumon Sattabongkot, Alberto Moreno, and Mary R. Galinski. 2019. JCI Insight.; 4(9). pii: 125156. doi: 10.1172/jci.insight.125156.

Database offers tool for global health collaborations

 

As the big data revolution continues to evolve, access to data that cut across many disciplines becomes increasingly valuable. In the field of public health, one barrier to sharing data is the need for users to fully comprehend complex methodological details and data variables in order to properly conduct analyses.

The Clinical Epidemiology Database, ClinEpiDB.org, aims to address these barriers by not only providing access to huge volumes of data, but also providing tools to help interpret complex global epidemiologic research studies. The development of ClinEpiDB has been led by the University of Georgia’s Institute of Bioinformatics, University of Pennsylvania’s School of Arts and Sciences and its Perelman School of Medicine, and the University of Liverpool’s Institute of Integrative Biology.

On March 7, ClinEpiDB released data, methodology and documentation from “The Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development” (MAL-ED) study. The MAL-ED study represents a nearly decade-long research collaboration between the Foundation for the National Institutes of Health (FNIH), Fogarty International Center, and an international network of investigators.

The MAL-ED study was designed to help identify environmental exposures early in a child’s life that are associated with shortfalls in physical growth, cognitive development, and immunity. The study characterizes gut function biomarkers on the causal pathway from environmental exposure to growth and development deficits and assesses diversity across geographic locations with respect to exposures and child health and development. The MAL-ED consortium has published a significant library of peer-reviewed publications and ClinEpiDB now makes the MAL-ED data highly visible and accessible in new and exciting ways.

“It is great to see how investments and effort directed at data being Findable, Accessible, Interoperable and Reusable—i.e., F.A.I.R—are beginning to bear fruit,” said Jessica Kissinger, UGA Distinguished Research Professor of Genetics and co-principal investigator on the Bill & Melinda Gates Foundation award that funded the ClinEPi Development. “Too many important studies are buried in the scientific or medical literature and not easily accessible or reusable in moving the frontier in the important battles related to infectious disease and human health. This multi-institutional, multiple-funder, interdisciplinary approach is working.”

ClinEpiDB is also home to the Global Enteric Multicenter Study (GEMS) which contains data from more than 22,000 children from seven sites in South Asia and Africa and was the largest-ever study to investigate the causes to moderate-to-severe diarrheal illness in children in lower- to middle-income countries. The most recent ClinEpiDB release also contains data from GEMS1A, a continuation of the GEMS study that broadened its scope to include less-severe diarrheal episodes. The addition of MAL-ED adds to the growing resource of high-quality maternal and child global health data.

“Over 10 years, our international network of investigators collaborated through MAL-ED to better understand the complicated relationships among intestinal infections, nutrition and other environmental exposures on child development,” said Michael Gottlieb, FNIH deputy director of science (retired) and lead PI for the MAL-ED study. “The MAL-ED Network generated a high-quality data set, possibly the largest of its kind, on various research areas from cognitive abilities to gut function to immunological response. We are pleased to make this dataset available through ClinEpiDB so it can be used by researchers far into the future to increase scientific understanding, test new research hypotheses and design and implement better intervention strategies to reduce childhood morbidity and mortality.”

MAL-ED sites (located in Iquitos, Peru; Fortaleza, Brazil; Haydom, Tanzania; Limpopo, South Africa; Bhaktapur, Nepal; Naushero Feroze, Pakistan; Vellore, India; Dhaka, Bangladesh) allowed for comparisons to be made among and between children living in geographically and culturally diverse urban and rural environments and in countries at different levels of economic development.

MAL-ED data in ClinEpiDB account for over 1.3 million observations covering anthropometrics, nutrition, vaccination status, diarrheal and respiratory disease episodes and countless other details collected by community field workers in 2009-2014. The current release includes longitudinal data from children followed two times a week for the first 24 months of life.

Future data releases will contain data for some children up to 5 years of age. ClinEpiDB allows users to walk through these data easily via an intuitive interface, enabling point-and-click filtering, simple queries and more complex “search strategies.”

See https://youtu.be/535PcFrBH8M for a video introduction to this resource. ClinEpiDB will continue to grow and provide increased access to malaria and maternal and child health global datasets thus facilitating epidemiologic research in an open data environment while protecting patient identity.

Data boost: Using big data to fight disease

Jessica Kissinger

From leisure to health, digital databases can streamline nearly every facet of modern life.

Remember when making travel plans to a single destination took hours? Now booking flights, hotels and rental cars is just a few clicks—and a credit card—away thanks to travel sites like Expedia, Travelocity and others. Travelers get to compare competitors on price, amenities, customer reviews and proximity to popular locations. The sites pull together multiple data points from various sources (such as pricing from the seller, reviews from users, and maps from Google) and organize them for customers to view.

Jessica Kissinger, the director of UGA’s Institute for Bioinformatics and member of the Center for Tropical and Emerging Global Diseases, is doing for infectious disease research what travel sites did for vacation planning.

All over the world, researchers are racing to stop the spread of deadly and debilitating pathogens such as malaria. As those researchers and public health officials determine, or record data about a disease, Kissinger and her colleagues work to make that data accessible and searchable by the global research community for free.

“We take data generated by others and make them better,” says Kissinger, a Distinguished Research Professor of Genetics. More specifically, Kissinger and a team of cell biologists, geneticists and computer scientists pull disease data from a variety of sources, translate them into standard formats and make them searchable.

 

Jessica Kissinger, the director of UGA’s Institute for Bioinformatics, is doing for infectious disease research what travel sites did for vacation planning.

Enabling Discovery

How does building a database fight disease? Data help researchers construct and test their ideas about how to create treatments for diseases or map out ways to halt their spread.

“We don’t give them answers,” Kissinger says. “We give them a framework in which to generate and test hypotheses.”

Kissinger and her team have built databases to take on malaria and other infectious diseases such as toxoplasmosis, cryptosporidiosis and trypanosomiasis. They are also creating tools for studying childhood malnutrition and factors related to disease, and making them accessible to all as they become publicly available. These databases collectively service more than 70,000 unique users a month from more than 100 countries.

To put it simply, her work saves time. It speeds the pace discovery for the next possible solution, the next cure. Without these databases, researchers could spend weeks, months, even years researching existing literature on a disease in the library or recreating work in the lab.

Jessica Kissinger with student

These are tools by biologist for biologists … I think it is that sense of being a member of that community, having your finger on the pulse of what’s going on, that allows you to keep the tools useful. ~ Jessie Kissinger Director, Institute of Bioinformatics

Career Evolution

Kissinger didn’t set out to build databases.

She was trained as a molecular evolutionary biologist, not a computer scientist. “I like to see how molecules change over time,” she says. “When I started in school it was about how a gene or protein evolved.”

It turned out that her field was evolving too. Technology was allowing researchers to understand molecules through bigger data sets. Now, scientists aren’t just looking at individual genes but entire genomes, which are the complete sets of genes in a cell or organism.

As the field evolved, Kissinger learned and embraced the technology. Over time, she shifted her balance away from the so called “wet lab,” where she worked directly with the organisms, to focus mostly on the computer-based “dry lab.”

Her database work started with malaria and continued to expand.

“Now we make 10 different component databases for over 300 organisms (EuPathDB.org), a comparative database to see how conserved genes are across organisms and a new epidemiology database to study the prevalence, spread and factors related to disease in humans (ClinEpiDB.org).” she says.

Kissinger’s team relies on an expert advisory board that helps the researchers customize the databases for each disease community, so they have the largest impact on research. It helps that Kissinger started in a wet lab before diving into informatics.

“These are tools by biologist for biologists,” she says. “We have a lot of computer scientists in the middle, but I think it is that sense of being a member of that community, having your finger on the pulse of what’s going on, that allows you to keep the tools useful.”

 

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Originally published at https://greatcommitments.uga.edu/story/data-boost/