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Category: CTEGD Blog

Invited Speaker Spotlight: Marc-Jan Gubbels

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About the Speaker

Marc-Jan GubbelsMarc-Jan Gubbels received his Ph.D. at the University of Utrecht, the Netherlands, on diagnostics and vaccines for tick-transmitted Theileria and Babesia parasites of cattle. He then came to the CTEDG for a post-doc with Dr. Boris Striepen on Toxoplasma gondii. In 2005, he transitioned into an independent faculty position at Boston College and continued working on Toxoplasma. His lab is using and developing forward, reverse and functional genetic tools using enzymatic as well as fluorescent protein reporter assays in combination with cell sorting and fluorescence microscopy to learn more about the parasite’s cell biology.

Marc-Jan Gubbels’s Talk

Dr. Gubbels will give the following talk at 4:25 pm.

Of the Toxoplasma gondii Basal Complex Proteome: Cell Division, Apical Annuli and Beyond

Klemens Engelberg1, Suyog Chavan1, Tyler Bechtel2, Victoria Sánchez-Guzmán1, Allison Drozda1, Eranthie Weerapana2 and Marc-Jan Gubbels1
1Department of Biology, Boston College, Chestnut Hill, MA, 2Department of Chemistry, Boston College, Chestnut Hill, MA

Toxoplasma gondii replicates by an internal budding mechanism producing two daughter parasites per division round. Budding is driven by cortical cytoskeleton assembly and concludes with the actions of the basal complex (BC). Although the BC is reminiscent of the contractile ring in higher eukaryotes, its composition, mechanism and controls differ substantially. To deepen our insights in this unusual cytokinesis apparatus, we dissected its proteomic composition by reciprocal proximity-dependent biotinylation experiments (BioID). This identified numerous undefined proteins, several of which with critical roles in cell division, next to hints at multiple phosphorylation-based controllers. Next, we assembled a protein-protein interaction network using interaction probability predictions, which defined several sub-complexes as well as protein hubs connecting the complexes. Furthermore, temporal resolution across the budding process revealed components uniquely associated with BC initiation, its expansion and, surprisingly, its mature phase, hinting at functions beyond cell division. Serendipitously, some of the BC proteins were also present in the enigmatic apical annuli, which comprise 5-6 donut shaped structures toward the basal end of the cytoskeleton. Assessment of the annuli resolved their architecture and provided hints toward a function in internal budding, thereby highlighting an underappreciated aspect of cell division.

 

More information about the Molecular Parasitology & Vector Biology Symposium and the schedule of presentions are available on our website. The deadline to register for the symposium is April 24.

Invited Speaker Spotlight: Tiffany Weinkoff

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About the Speaker

Tiffany WeinkoffMacrophages are the major cell type infected by Leishmania parasites and the goal of my research is to define the relationship between Leishmania parasites, macrophages and the vasculature. Throughout my graduate studies and postdoctoral positions, I have dedicated my efforts toward understanding parasite-host interactions. As a graduate student at the University of Georgia carrying out research at the Centers for Disease Control and Prevention under Dr. Patrick Lammie, I was exposed to high caliber basic research in the CTEGD while simultaneously confronted with important public health issues in field settings related to neglected tropical diseases. My predoctoral research focused on the ability of monocytes to modulate lymphatic endothelial cell function and how this interaction contributed to the pathogenesis of human filarial disease. For my first postdoctoral position, I moved to the laboratory of Dr. Fabienne Tacchini-Cottier at the University of Lausanne in Switzerland. In Switzerland I gained experience using the mouse model to study the immunologic mechanisms involved in susceptibility to Leishmania infection. For my second postdoctoral position, I went to the laboratory of Phillip Scott at the University of Pennsylvania, a world-renowned professor and institution in the field of immunoparasitology. My initial project in the Scott lab, addressed the role of M2 macrophages as safe havens during Leishmania infection. For my second project in the Scott lab, I merged the knowledge and experience gained from my predoctoral research studying myeloid cells and vessels in filariasis with the technical experience of my first postdoctoral position to address the roles of innate cells in vivo in leishmaniasis. In the past months, I have transitioned to an Assistant Professor at the University of Arkansas for Medical Sciences (UAMS) where I have joined an elite group of vibrant and enthusiastic scientists with expertise in host-pathogen interactions. At UAMS, I am expanding upon previous studies examining vascular remodeling and the role of the VEGF-A/VEGFR-2 signaling pathway in lymphangiogenesis during Leishmania infection. In the future, I will work in collaboration with Dr. Camila Oliveira in Bahia, Brazil in a new project focusing on vascular remodeling during murine and human Leishmania braziliensis infection. These studies will provide important insights into our current understanding of the role of the vasculature during human disease.

Tiffany Weinkoff’s Talk

Dr. Weinkoff will give the following talk at 2:45 pm

The Role of Myeloid Cells in Vascular Remodeling during Leishmania major Infection

Tiffany Weinkopff
Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

Our lab investigates the mechanistic basis for the pathogenesis of disease driven by Leishmania, a protozoal parasite that causes cutaneous lesions. Following infection, lesion severity is often increased by an exaggerated inflammatory response. As a result, the inflammatory response can maintain disease even after the parasite infection has been controlled. Given vascular remodeling contributes to the magnitude of many inflammatory conditions, it is hypothesized that the manipulation of factors promoting angiogenesis or lymphangiogenesis would alter lesion severity in leishmaniasis. Our findings demonstrate that murine Leishmania major infection leads to dramatic changes in vessel morphology, number and permeability. At the peak of infection, VEGF-A and VEGFR-2 expression are upregulated and VEGFR-2 blockade led to a reduction in lymphatic endothelial cell proliferation and simultaneously increased lesion size without altering the parasite burden. We showed VEGF-A/VEGFR-2 signaling promotes lymphangiogenesis to restrict tissue inflammation in leishmaniasis. Given VEGF-A/VEGFR-2 signaling contributes to lesion resolution, we are currently investigating the cellular and molecular mediators driving VEGF-A production. We found that macrophages are the predominant cell type expressing VEGF-A during L. major infection and that parasites can directly induce VEGF-A production by macrophages in vitro. Given Leishmania parasites activate HIF-1α and this transcription factor induces VEGF-A expression, we analyzed the expression of HIF-1α during infection. We showed that macrophages are the major cell type expressing HIF-1α during infection and that parasite-induced VEGF-A production is mediated by HIF activation. We are presently examining VEGF-A expression in mice deficient in HIF signaling specifically in myeloid cells. To date, we have shown that LysMCre ARNTf/f mice express less VEGF-A than LysMCre ARNTf/+ control mice following infection, and we are exploring how decreased myeloid VEGF-A production influences vascular remodeling and lesion resolution in these animals. Altogether, these studies suggest macrophage HIF-dependent VEGF-A production contributes to lymphatic remodeling during L. major infection.

 

More information about the Molecular Parasitology & Vector Biology Symposium and the schedule of presentions are available on our website. The deadline to register for the symposium is April 24.

Invited Speaker Spotlight: James Morris

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About the Speaker

James MorrisJames Morris is currently a Professor of Genetics and Biochemistry at Clemson University.  He earned his BS at The College of William and Mary in Williamsburg VA in 1990 and an M.S. in Entomology at the University of Georgia in Athens GA in 1992.  He completed his Ph.D. in Cellular Biology at the University of Georgia in 1997, characterizing the enzymology of a glycosylphosphatidylinositol phospholipase C from the African trypanosome, Trypanosoma brucei, under the supervision of Dr. Kojo Mensa-Wilmot.  Following his Ph.D., Jim moved to Baltimore MD to work in the laboratory of Dr. Paul T. Englund, where he was part of the team that developed the first RNAi-based library for forward genetics in any organism – in this case, the African trypanosome.  As part of this work, the team developed the vector pZJM (Jim is the “J”) that is still widely used for silencing genes in the parasite.

In 2003, Jim moved to Clemson University as an Assistant Professor in the Department of Genetics and Biochemistry, where he has remained to date.  His team has focused on resolving the mechanisms that protozoan parasites use to sense and metabolize the important sugar glucose during infection of their human host.  Through these studies, parasite-specific components of the sugar sensing and uptake pathway have been identified and, in an on-going collaborative effort, small molecule inhibitors of the pathways with anti-parasitic activity have been developed.  While his team has historically focused on the African trypanosome, more recent work on the malaria parasite Plasmodium falciparum and the brain-eating amoeba Naegleria fowleri suggests that exploiting the sugar metabolism pathways of these single-celled invaders may also prove useful in the development of new therapeutics.

James Morris’s Talk

Dr. Morris will give the following talk at 12:05 pm.

Pour Some Sugar on Me: Glucose, Development, Drug Discovery, and the African Trypanosome

James C. Morris
Eukaryotic Pathogens Innovation Center, Clemson University

Glucose is critical for the infectious blood stages of the African trypanosome, Trypanosoma brucei, serving as both a key metabolic agent and an important signaling molecule. While lack of the hexose is toxic to the proliferative long slender life stage of the parasite, the absence of glucose initiates differentiation in the non-dividing short stumpy (SS) form. These parasites demonstrate hallmarks of development into the next lifecycle stage, the procyclic form (PF) parasite, that include resumption of growth and expression of PF-specific antigens. Both SS differentiation and the growth of the resulting PF parasites is inhibited by glucose and non-metabolizable glucose analogs, with the latter observation suggesting a potential receptor-mediated mechanism for perception of the sugar. The importance of the hexose to the parasite for both metabolic a developmental needs suggests that glucose uptake or distribution inhibitors would be potentially useful anti-parasitic compounds. To identify small molecule inhibitors of glucose acquisition, we developed parasites that endogenously express FRET-based protein glucose sensors in the cytosol or glycosomes. Using these cells, we have completed a 25,000-compound pilot screen and have identified inhibitors with useful medicinal chemistry properties that have potential as a new line of lead compounds against the parasite.

 

More information about the Molecular Parasitology & Vector Biology Symposium and the schedule of presentions are available on our website. The deadline to register for the symposium is April 24.

Invited Speaker Spotlight: Matthew Collins

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About the Speaker

Matt CollinsMatthew Collins obtained his Ph.D. studying under mentor Dr. Rick Tarleton at the University of Georgia; his thesis project focused on the role of CD8+ T cells in controlling chronic T. cruzi in nonlymphoid tissue. During Infectious Diseases fellowship at the University of North Carolina, he worked with Dr. Aravinda de Silva to study specificity and cross-reactivity of human antibody responses to flaviviruses such as dengue and Zika virus. He is now an Assistant Professor at Emory University where he leads a translational arbovirology research program. Goals of the group are to understand basic aspects of human adaptive immune responses to sequential related viral infection and to develop and implement serologic tools to support epidemiologic studies and the development of vaccines and diagnostic tests.

Matt Collins’s Talk

Dr. Collins will present the following talk at 9:55 am.

Epitope Targets of the Human Antibody Response to Zika Virus Infection

Matthew H. Collins1,2, Huy A. Tu3,4, Ciara Gimblet-Ochieng5, Guei-Jiun Alice Liou5, Ramesh S. Jadi5, Stefan W. Metz5, Ashlie Thomas5, Benjamin D. McElvany4, Edgar Davidson6, Benjamin J. Doranz6, Yaoska Reyes7, Natalie M. Bowman2, Sylvia Becker-Dreps8, Filemón Bucardo7, Helen M. Lazear5, Sean A. Diehl3,4, Aravinda M. de Silva5
1Department of Medicine, Emory University 2Department of Medicine, University of North Carolina-Chapel Hill 3Cellular, Molecular, and Biomedical Sciences Program, University of Vermont 4Department of Microbiology and Molecular Genetics, University of Vermont 5Department of Microbiology and Immunology, University of North Carolina 6Integral Molecular, Inc. 7Department of Microbiology, National Autonomous University of Nicaragua 8Departments of Family Medicine and Epidemiology, University of North Carolina-Chapel Hill

Zika virus (ZIKV) transmission became a global public health emergency after the recent epidemic in Latin America and beyond revealed rare but dire manifestations of infection such as severe birth defects and Guillain-Barré syndrome. The emergence of ZIKV in areas where other related flaviviruses such as dengue are endemic creates challenges in accurately diagnosing infections, conducting reliable surveillance, as well as in understanding the distinguishing aspects of the host immune response to ZIKV due to antibody (Ab) cross-reactivity. Because vaccines represent a key strategy for prevention of infectious diseases and typically rely on robust antibody responses, we sought to analyze the durable antibody responses in individuals infected by ZIKV as a first flavivirus infection. We observed complex populations of antibodies that bind to epitopes on intact virions, simpler epitopes on envelope protein monomers as well as envelope subdomains. Moreover, strong neutralizing antibody responses that minimally cross-react with dengue viruses were consistently detected. To better understand the molecular determinants of the neutralizing antibody response to ZIKV and to develop tools that could aid vaccine development, we isolated two potently neutralizing monoclonal antibodies (mAbs) from one primary ZIKV case and mapped key amino acid residues involved in mAb binding and neutralization by multiple complimentary methods including generation of neutralization escape mutants and alanine scanning mutagenesis. The mAbs recognize different epitopes centered on domain I and domain II of the viral envelope protein. Functionally, both mAbs were protective in a lethal mouse model of ZIKV infection. Ongoing work is examining the prevalence of these specific Ab responses at the population level. This work provides new knowledge and tools that may be useful as diagnostic reagents or as therapeutics and will advance vaccine development.

 

More information about the Molecular Parasitology & Vector Biology Symposium and the schedule of presentions are available on our website. The deadline to register for the symposium is April 24.

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.

Order Your CTEGD Shirts by April 23

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Now is your chance to get a short sleeve shirt, long sleeve shirt, and/or a sweatshirt with CTEGD’s logo. Orders must be placed by April 23. If you are attending the symposium or would like to pick up your shirt at UGA, then choose “Pickup at Shirtworks” at checkout. We will pick up the shirts for distribution at the Molecular Parasitology & Vector Biology Symposium on May 1. Any shirts not picked up at the symposium will be available in the CTEGD main office in Coverdell Center.

If you are outside of UGA and not attending the symposium, you can have your order shipped directly to you.

Your purchase of a shirt supports the activities of CTEGD. Place your order TODAY: http://bit.ly/2V9wqNn

Register Now! Molecular Parasitology & Vector Biology Symposium

Symposium 2019 announcement

Registration is now open for the 29th Annual Molecular Parasitology & Vector Biology Symposium hosted by the Center for Tropical and Emerging Global Diseases. It will be held on Wednesday, May 1, 2019, at The Georgia Center on the University of Georgia campus in Athens, GA.

This day-long regional conference on parasites and host/parasite interaction draws more than 200 attendees from many departments at UGA and colleagues from other institutions throughout the United States.

As CTEGD is celebrating its 20th anniversary, 4 outstanding alumni have been invited to give spotlight presentations throughout the day in addition to the oral presentations from graduate students, postdocs, and senior researchers.

 

Invited Alumni Speakers:

 

  • James Morris, mentored by Kojo Mensa-Wilmot, is a professor in the Department of Genetics and Biochemistry at Clemson University.

 

  • Matthew Collins, mentored by Rick Tarleton, is an assistant professor in the Division of Infectious Diseases at Emory University School of Medicine

 

  • Tiffany Weinkopff, mentored by Patrick Lammie, is an assistant professor in the Department of Microbiology and Immunology at the University of Arkansas’s College of Medicine.

 

  • Marc-Jan Gubbels, mentored by Boris Striepen, is a professor in the Department of Biology at Boston College.

 

Oral and Poster Presentations

Graduate students, postdoctoral fellows, and other researchers are invited to present their research in either an oral or poster presentation. Abstracts for these presentations are due by April 12. During registration, please select Poster or Speak. An email will be sent to you with instructions on submitting your abstract. Please keep the following in mind when preparing your submission:

 

  • All abstracts must be submitted online by April 12, 2019, via the link in the email you received after registering.
  • Abstracts should include Title, Author(s), and Affiliation(s).
  • Abstracts should be 300 words or less, excluding title, author(s), and affiliation(s).
  • Notification of submission will be emailed to you.
  • Note: there has been issues of special characters (i.e. α and γ) not displaying in the submitted abstract. Therefore, please note the use of special characters by spelling out the word next to the symbol, e.g. IFN-γ (gamma) or β (Beta). The correction will be made during the editing process.
  • Abstracts will be published online by Wednesday, April 24.

 

Cost & Register

There is no cost to attend the Symposium or the full catered lunch, but registration is required.

Hotel Rooms: For those wishing to stay overnight, reservations can be made at The Georgia Center Hotel. The Holiday Inn is also nearby.

 

Register here: http://register.ctegd.uga.edu/

For more information: https://ctegd.uga.edu/events/symposium/

$1.5 million initiative to upgrade labs across campus

Michael Strand
A $1.5 million initiative to upgrade labs across campus is enabling faculty members such as Regents Professor Michael Strand to enhance their research productivity. (Photo by Dorothy Kozlowski/ UGA)

Athens, Ga. – Labs and research support spaces across campus will be getting an upgrade, thanks to a $1.5 million presidential initiative that seeks to build on the university’s dramatic growth in research activity.

Presidential renovation funds have been distributed to nine schools and colleges and will be used to upgrade labs and replace core equipment that enables faculty members to conduct research and be more competitive in seeking grant funding. Proposals were solicited from deans and chosen based on links to college and university strategic priorities, as well as implications for faculty recruitment efforts and grant funding opportunities.

 

“To advance the research mission of the university and attract and retain outstanding faculty, we must support state-of-the-art facilities that assist the faculty with their groundbreaking work,” said President Jere W. Morehead. “I am pleased the institution has been able to help several faculty with critical needs, thanks to this initiative.”

In the College of Agricultural and Environmental Sciences, an upgrade to an insectary that will be used to rear mosquitoes will enable Regents’ Professor and National Academy of Sciences member Michael Strand and several of his colleagues in the department of entomology to expand their research on infectious diseases such as malaria and dengue fever. “We’re going to be able to do a whole series of experiments that we currently can’t do,” Strand said, adding that the upgraded facility opens up new opportunities for grants.

Upgrades to the Sensory Evaluation and Product Development Lab in the College of Family and Consumer Sciences will enable assistant professor Ginnefer Cox to develop and evaluate new food product formulations more efficiently while also giving students hands-on experiences and facilitating industry partnerships. “This new space is going to have equipment that helps train students to be the next product developers,” Cox said. “The upgrades also create more opportunities to collaborate in research with food companies, which opens up opportunities for students to interact with them and obtain internships and permanent employment.”

In the department of physics and astronomy, part of the Franklin College of Arts and Sciences, renovation funds will aid in faculty recruitment by modernizing an outdated laboratory. “We’re really excited to have received this funding,” said department head Phillip Stancil. “The space has been unused for the last several years, and with this renovation it’ll be ready for a new experimentalist to move in.”

Other schools and colleges that have received funding through presidential renovation funds are the College of Engineering, College of Environment and Design, Odum School of Ecology, College of Public Health, College of Veterinary Medicine and the Warnell School of Forestry and Natural Resources.

Interim Senior Vice President for Academic Affairs and Provost Libby V. Morris noted that the lab renovation funds come at a time when sponsored research awards have increased by 34 percent over the past five years. It also coincides with recruitment initiatives that will bring up to 25 new faculty members to campus.

 

“Research activity at the University of Georgia has grown significantly in recent years, with strategic investments in faculty and facilities enabling discoveries that point the way to a healthier and more promising future,” Morris said.

Writer: Sam Fahmy, 706-583-0727, sfahmy@uga.edu