A Wayne State University School of Medicine student and two recent graduates working on a collaborative project in the laboratories of Associate Professors of Ophthalmology, Visual and Anatomical Sciences Ashok Kumar, Ph.D., and Ryan Thummel, Ph.D., have discovered that zebrafish dont contract endophthalmitis.

The eye infection can cause blindness within hours if not diagnosed and treated quickly.

Matthew Rolain, Frank Mei, M.D. 19 and Xiao Yi Zhou, M.D. 17, contributed to the study, Zebrafish are Resistant to Staphylococcus aureus Endophthalmitis, published in Pathogens, a peer-reviewed journal in the field of microbiology and immunology.

The study showed that while humans require only 10 to 100 bugs to cause endophthalmitis, and mice require 5,000 before infection, in the freshwater fish even 250,000 bacteria wont cause the eye infection. The finding indicates that zebrafish eyes are incredibly resistant to such eye infections and possess strong host defense mechanisms.

Dr. Thummel and others in the field have shown that humans and fish share similarities in eye structure and immune responses. Studying why fish, but not human eyes, are resistant, may help identify protective pathways and molecules that could be translated to humans.

Traditionally, we have used a mouse model to study the pathobiology of these infections. In recent years, zebrafish have emerged as an important model organism in biomedical research, providing insight into the pathogenic mechanisms of infectious diseases. We sought to determine their susceptibility with the ocular bacterial infection, Dr. Kumar said. I contacted my colleague Dr. Thummel and discussed the idea, and the project took off with participation of three medical students who completed the task collectively.

Dr. Kumars laboratory focuses on understanding the pathobiology of ocular infections, especially those affecting the retina, such as endophthalmitis. The infection most often occurs due to surgical complications or eye trauma.

Apart from conducting research, I truly enjoyed mentoring these medical students, Dr. Kumar said. I hope they continue develop scientific acumen as they transition to their respective residency programs.

Matthew Rolain will graduate from the School of Medicine in 2020.

Working with Dr. Kumar and Dr. Thummel was an awesome experience, he said. They gave me great guidance and were always very supportive, regardless of the outcome of our experiments. It was nice being able to learn about the research process while working on such an interesting and potentially impactful project. Hopefully the scientific community will be able to build on our results to better help future patients.

Dr. Mei is now a resident in his transitional year in Chicago before starting a two-year Ophthalmology program at the University of Texas Southwestern Medical School in Dallas.

Individually, Drs. Kumar and Thummel were well respected in their separate expertise. However, the unification of their talents into a singular project created a collaborative environment where the strengths of both labs meshed, launching and dramatically expeditingthis project to completionin a very short timeframe. Bridging the gap between Scott Hall and the KresgeEye Institute, Drs. Kumar and Thummel created a warm atmosphere to foster my growth as a researcher. This experience was invaluableand an encouragement for me to seek further collaborations in my career in academic ophthalmology, Dr. Mei said.Lastly,I would like to thank the Medical Summer Research Project through Wayne State and the Kresge Summer Internship for supporting me through this project.

Their colleague, Dr. Zhou is a resident in her transitional year at NorthShore University Health System in Illinois. She completed a one-year fellowship at Bascom Palmer Eye Institute in Miami after graduation.

Moving forward, they plan to test zebrafish susceptibility to other bacterial and fungal pathogens.

The work was supported by grants from the National Institutes of Health (R01EY027381 and R01EY026964 to Dr. Kumar, and R01EY026551 to Dr. Thummel. Histology and imaging core resources were supported by a vision core grant (P30EY04068) and an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, Visual and Anatomical Sciences.

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Medical student and alumni discover zebrafish are resistent to eye infection - The South End

Manizheh Narimani,1 Mohammadreza Sharifi,2 Ali Jalili1

1Cancer and Immunology Research Center, Institute of Research for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran; 2Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Correspondence: Ali JaliliCancer and Immunology Research Center, Institute of Research for Health Development, Kurdistan University of Medical Sciences, Sanandaj, IranTel +98-9183771862Email Ali130@gmail.com

Introduction: Human Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) which encodes survivin exhibits multiple biological activities, such as cell proliferation and apoptosis. Survivin is overexpressed in numerous malignant diseases including acute myeloid leukemia (AML). Recent studies have shown that the CRISPR/Cas9 nuclease-mediated gene-editing systems are suitable approachsfor editing or knocking out various genes including oncogenes.Methods and materials: We used CRISPR-Cas9 to knockout the BIRC5 in the human leukemic cell line, HL60, and KG1, and these cell lines were transfected with either the Cas9- and three sgRNAs expressing plasmids or negative control (scramble) using Lipofectamine 3000. The efficacy of the transfection was determined by quantitative reverse transcription-polymerase chain (RT-qPCR) and surveyor mutation assays. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively.Results: We have successfully knocked out the BIRC5 gene in these leukemic cells and observed that the BIRC5-knocked out cells by CRISPR/Cas9 showed a significant decrease (30 folds) of survivin at mRNA levels. Moreover, cell death and apoptosis were significantly induced in BIRC5-CRISPR/Cas9-transfected cells compared to the scramble vector.Conclusion: We demonstrated for the first time that targeting BIRC5 by CRISPR/Cas9 technology is a suitable approach for the induction of apoptosis in leukemic cells. However, further studies targeting this gene in primary leukemic cells are required.

Keywords: BIRC5, survivin, CRISPR/Cas9 nuclease, AML, KG1 cells, HL60 cell

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Knockout Of BIRC5 Gene By CRISPR/Cas9 Induces Apoptosis And Inhibits C | BLCTT - Dove Medical Press

University of Iowa professor Gail Bishop has been named a fellow of the American Association for the Advancement of Science (AAAS), the worlds largest general-scientific society and publisher of the journal Science. Election as an AAAS Fellow is an honor bestowed upon AAAS members bytheirpeers.

As part of the Biological Sciences Section, Bishop,a professor of microbiology and immunology at the UI Roy J. and Lucille A. Carver College of Medicine, was selected for her distinguished contributions to the field of immunology, particularly for insights into regulation of T and B lymphocyteactivation.

This year, 443 members were awarded this honor by the AAAS because of their scientifically or socially distinguished efforts to advance science or itsapplications.

I am very honored by this recognition from my scientific colleagues,says Bishop, who also is associate director for basic science research at Holden Comprehensive Cancer Center at the UI, and a professor of internalmedicine.

Bishop joined the UI in 1989. Her research focuses on the molecular mechanisms that regulate the function of blood cells known as lymphocytes in normal immunity, inflammatory disease, and cancer. In particular, Bishop and her team are investigating lymphocyte signaling and interactions between innate and adaptive immune receptors. Her work has implications for treating B-cell cancers, including multiple myeloma, and developing cancervaccines.

She received a doctoral degree in cellular and molecular biology from the University of Michigan in 1983 and performed postdoctoral research at the University of North Carolina, Chapel Hill, focusing on understanding the molecular mechanisms of B lymphocyte activation and interactions between B cells and Tcells.

Bishop has served in many roles during her 30-year UI career. She was appointed as endowed College of Medicine Distinguished Professor of Microbiology in 2001 and Holden Chair of Cancer Biology in 2004; from 1998 to 2013, she directed the Immunology Graduate Program; and in 2004, she was appointed associate director for basic science research of Holden Comprehensive CancerCenter.

This is such a well-deserved honor for Dr. Bishop, who exemplifies the values that we believe make the University of Iowa great, says Brooks Jackson, UI vice president for medical affairs and the Tyrone D. Artz Dean of the UI Carver College of Medicine. As her election to the AAAS demonstrates, she is an established leader in her field of immunology, and she has coupled that scientific success with a deep commitment to training and mentoring the next generation of scientists. Her leadership within our research community has helped to shape an environment where collaboration and collegiality are valued andfostered.

Bishop also is the recipient of many awards and honors for service to the field of immunology. She served as both a section editor of The Journal of Immunology, and is on the current editorial board of the Journal of Leukocyte Biology. She has served as a grant reviewer for the National Science Foundation, the American Heart Association, and the National Institutes of Health, serving as chair of the NIH Tumors, Tolerance and Transplantation studysection.

In 2003, she received the UI Graduate Mentoring Award, and in 2009 was awarded the Iowa Technology Associations Woman of Innovation award for academic research innovation and leadership. Bishop served as president of the American Association of Immunologists in 201213, and is the director of the UI Center for Immunology and Immune-Based Diseases. She was elected as a Distinguished Fellow of the American Association of Immunologists in2019.

This years AAAS Fellows will be formally announced in the AAAS News and Notes section of the journal Science on Nov.29.

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Bishop named 2019 fellow of the American Association for the Advancement of Science - Iowa Now

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Newswise Structural immunologist Dr. Erica Ollmann Saphire is available to discuss Lassa virus and current efforts to develop much-needed antibody therapies to treat often lethal Lassa infections.

A Dutch doctor, who was evacuated from Sierra Leone after contracting Lassa fever, died on November 23, while being treated at Leiden University Medical Center. A second Dutch doctor and a Sierra Leonean anesthetist have also been infected. Other Dutch and British medical personnel have been evacuated.

Lassa typically causes flu-like symptoms but can be deadly in about a quarter of infected people. There is no vaccine.

Earlier this year, Dr. Ollmann Saphire and her team identified the molecular properties shared by antibodies that are particularly efficient at inactivating Lassa virus. The beauty of structural biology is that it gives you the ability to directly see how these therapies work, says Dr. Ollmann Saphire. These high-resolution images become blueprints to engineer potent antibody therapeutics or a vaccine that elicits the desired immune response.

Bio:

Erica Ollmann Saphire, Ph.D. is a Professor of the La Jolla Institute for Immunology. Her research explains, at the molecular level, how and why viruses like Ebola and Lassa are pathogenic and provides the roadmap for medical defense. Her team has solved the structures of the Ebola, Sudan, Marburg, Bundibugyo and Lassa virus glycoproteins, explained how they remodel these structures as they drive themselves into cells, how their proteins suppress immune function and where human antibodies can defeat these viruses.

Dr. Ollmann Saphire also directs the Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC), which unites 43 academic, industrial and government labs across five continents. The consortiums goal is to understand which antibodies are most effective in patients and to streamline the research pipeline to provide antibody therapeutics against Ebola, Marburg, Lassa and other viruses.

Dr. Ollmann Saphire is available via email, phone and Skype.

Watch Dr. Ollmann Saphire discuss Ebola in the Democratic Republic of Congo.

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Expert available to discuss Lassa virus and antibody therapies against the virus - Newswise

Surprisingly, the antiviral cytokine type I interferon (IFN-I) was found to be a master regulator of metabolic pathways in liver cells. The researchers focused on the urea cycle, a central metabolic node, and found that it is disrupted by IFN-I during viral infection. This led to altered serum metabolite concentrations which regulated antiviral immunity and reduced liver pathology.

The liver is a crucial organ for systemic metabolism in our body. Apart from the turnover of biomolecules and drug metabolism, the liver's main function is the removal of toxic substances from the organism. Hepatocytes, or liver cells, are the most abundant cell type and functional unit of the liver. They are metabolic powerhouses in the healthy organism, but they also serve as important immune signaling platforms during infections. As such, they have the potential to react to a range of cytokines - small molecules that are essential for the coordination of immune responses.

Previous studies in the field of immunology and metabolism, or immunometabolism, unveiled groundbreaking mechanisms about how cells of the immune system need to adjust their metabolism to perform their functions to fight pathogens and cancer. Building on this, Andreas Bergthaler and his group at CeMM aimed to study the immunometabolic changes that occur in the whole organism during infection. They particularly focused on the liver due to its important role in controlling systemic metabolism.

To dissect the involved complex processes, the authors took advantage of the benchmark model of chronic infection, the lymphocytic choriomeningitis virus (LCMV). Research with LCMV had already led to fundamental insights into immunology over the past 80 years, and notably contributed to three Nobel Prizes. Among them is the 2018 Nobel Prize in Physiology or Medicine, which was awarded to James Allison and Tasuku Honjo for their discoveries relating to the revolutionary new cancer immunotherapies which exploit the body's own immune killer cells, or CD8 T cells.

The present study by Alexander Lercher, Anannya Bhattacharya et al. is the result of cross-disciplinary collaborations with researchers from the Medical University of Vienna and the University of Veterinary Medicine in Vienna (Austria), as well as from the Hannover Medical School (Germany), the Cantonal Hospital St. Gallen (Switzerland) and the company Bio-Cancer Treatment International Ltd (China). The study was designed as an integrative unbiased approach to investigate the molecular changes in the liver during chronic infection. Next to expected inflammatory changes, the authors identified intriguing changes in hepatocyte metabolism. Many central metabolic pathways, among them the urea cycle, were found to be repressed upon infection. The urea cycle is essential to remove toxic ammonia from the body to prevent brain damage. Surprisingly, the researchers identified the antiviral cytokine signaling pathway of type I interferons (IFN-I) as a regulator of the urea cycle. This resulted in altered blood concentrations of the amino acids arginine and ornithine. "A key experiment for us was that when we removed the receptor for IFN-I on the surface of hepatocytes, we didn't see these metabolic changes anymore", says Alexander Lercher, first author of the study and PhD student in the laboratory of CeMM Principal Investigator Andreas Bergthaler. The systemic changes of arginine and ornithine were found to inhibit antiviral CD8 T cell responses and to reduce liver damage.

One of the most important revelations of this study was the identification of IFN-I signaling as a master regulator for the repression of metabolic processes in hepatocytes upon infection. "We were really surprised that an antiviral molecule affects such vital biological processes as the urea cycle during infection", says Michael Trauner, co-author of the study and head of the Department of Gastroenterology and Hepatology at the Medical University of Vienna. Together, these findings shed new light on how the body's immune system evolved to regulate liver metabolism that modulate CD8 T cell responses and reduce collateral tissue damage during infection. Andreas Bergthaler: "We regard this study an important contribution to the field of systemic immunometabolism. It also highlights the central role of the liver for our immune system and how organs of the body communicate through metabolites." In the future, such findings may be exploited to therapeutically intervene with the regulation of metabolic processes to modulate CD8 T cell responses in diverse diseases such as infection, cancer and autoimmunity.

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Immunity -- master regulator of liver metabolism identified during infection - Science Codex