関連学術集会・講演・シンポジウム

13 December 2024 | Shirokanedai (IMSUT)

学友会セミナー   2024年12月13日（金）東京大学医科学研究所

14:00 — 15:00  ２号館大会議室

Cheri Sirois, Ph.D
Cell Press・Scientific editor

Publishing your work: advice from a scientific editor
Have you ever wondered what happens to your paper after you submit it to a journal? This talk will give you an idea of what editors are looking for in your paper, and how to get the most out your conversations with editors at Cell Press journals. We will discuss how journals think about impact and conceptual advances, as well as how we balance the views of reviewers and other factors that lead to a decision to publish a paper. There will be plenty of time to discuss and answer questions, too! This talk welcomes professors, research scientists, and students—anyone who would like to better understand how to work with an editor to publish their studies. 

世 話 人 ： 〇佐藤佳（システムウイルス学分野）三宅健介（感染遺伝学分野）　　　　　　　　　　　　　　　　　　

6 December 2024 | Shirokanedai (IMSUT)

学友会セミナー   2024年12月6日（金）東京大学医科学研究所

9:30 — 11:00  1号館　講堂/ Auditorium, 1st building, The Institute of Medical Science

Roland Lang

Microbiological Institute – Clinical Microbiology, Immunology and Hygiene Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg・Professor

The ACOD1-itaconate pathway in intracellular bacterial infection: an immune-metabolic swiss army-knife to kill invaders and balance macrophage activation?
Specialized intracellular bacteria establish a niche within macrophages, to persist for long time and to reactivate replication in some individuals. My lab aims to understand how sensing of intracellular bacteria such as Mycobacterium tuberculosis and Coxiella burnetii generates protection through the induction of anti-microbial effector mechanisms. C. burnetii causes Q fever, which can lead to chronic infection of the vascular system with high lethality. We established a mouse model of persistent C. burnetii infection in Myd88-/- mice, in which we identified candidate genes involved in protection. Induction of ACOD1, the enzyme producing the immuno-metabolite itaconate, was essential to prevent C. burnetii replication in macrophages in vitro and in vivo. Itaconate directly inhibits the replication of C. burnetii at concentrations achieved in activated macrophages. Treatment of ACOD1-deficient macrophages and mice restored control of C. burnetii infection. These findings establish ACOD1-itaconate as essential early defense mechanism during Q fever. Itaconate, its endogenous isomers and its chemical derivatives have diverse effects on immune cell activity. Open questions on the anti-microbial and immunoregulatory effects and mechanisms of itaconate, as well as its therapeutic potential will be discussed. 

 世 話 人 ： 〇小檜山康司 (ワクチン科学分野)   Niloufar Kavian（マラリア免疫学分野） 　　

11:00 — 12:30   1号館　講堂/ Auditorium, 1st building, The Institute of Medical Science

Ed Lavelle

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin・Professor

Adjuvants strategies for injectable and mucosal subunit vaccines

Specialized intracellular bacteria establish a niche within macrophages, to persist for long time and to reactivate replication in some individuals. My lab aims to understand how sensing of intracellular bacteria such as Mycobacterium tuberculosis and Coxiella burnetii generates protection through the induction of anti-microbial effector mechanisms. C. burnetii causes Q fever, which can lead to chronic infection of the vascular system with high lethality. We established a mouse model of persistent C. burnetii infection in Myd88-/- mice, in which we identified candidate genes involved in protection. Induction of ACOD1, the enzyme producing the immuno-metabolite itaconate, was essential to prevent C. burnetii replication in macrophages in vitro and in vivo. Itaconate directly inhibits the replication of C. burnetii at concentrations achieved in activated macrophages. Treatment of ACOD1-deficient macrophages and mice restored control of C. burnetii infection. These findings establish ACOD1-itaconate as essential early defense mechanism during Q fever. Itaconate, its endogenous isomers and its chemical derivatives have diverse effects on immune cell activity. Open questions on the anti-microbial and immunoregulatory effects and mechanisms of itaconate, as well as its therapeutic potential will be discussed. 

世 話 人 ： 〇小檜山　康司 (ワクチン科学分野) Niloufar Kavian（マラリア免疫学分野） 　　　

13:30 — 14:30  ２号館大会議室/ Building. 2 Main Conference Room, The Institute of Medical Science

Vineet D. Menachery

Emory University・Associate Professor

Defining Spike Correlates of Coronavirus Emergence

The coronavirus spike has two major functions in the virus life cycle: receptor binding/attachment and entry/fusion via proteolytic activation. While most CoV emergence research focuses on receptor binding capacity, we believe that changes in proteolytic activation of spike is critical for zoonotic strains to become epidemic CoVs. Proteolytic activation is governed by motifs in the C-terminal of S1 (CTS1). This domain, adjacent to the receptor binding domain (RBD), harbors the S1/S2 cleavage site. A host protease in the endosome or on the cell surface must cleave this site to provide allow cleavage of S2 cleavage site leading to activation of fusion. Importantly, numerous CTS1 motifs contribute directly and indirectly to proteolytic activation of the spike. Our studies focus on changes in three areas of the CTS1: 1) the S1/S2 cleavage motif, 2) the region adjacent to the S1/S2 cleavage motif, and 3) changes in the CTS1 distal to the cleavage site. We believe that changes in these three areas help transition zoonotic CoVs to epidemics.  Defining the key motifs and understanding their mechanisms are a key to classify the threat posed by circulating zoonotic coronaviruses and respond to future CoV pandemics.

世 話 人 ： 〇 佐藤　佳（システムウイルス学分野）　 小檜山　康司（ワクチン科学分野）

14:30 — 15:30 ２号館大会議室/ Building. 2 Main Conference Room, The Institute of Medical Science

Angela L. Rasmussen

University of Saskatchewan・Professor

Host-Focused Approaches to Investigating Virus Emergence

Zooanthroponosis is a major threat to global human and animal health. Zooanthroponotic transmission of SARS-CoV-2 has occurred multiple times throughout the pandemic in numerous animal species that are susceptible to infection. SARS-CoV-2 likely originated from zoonotic spillover associated with live animal sales at the Huanan Seafood Market in Wuhan, China. In addition, there have been global reports of SARS-CoV-2 “spillback” into and subsequent transmission among wild, captive, and domesticated nonhuman animal species, including farmed mink, companion animals, captive animals, and wildlife. However, these discoveries have typically been incidental and there has been no systematic study of species-specific susceptibility to SARS-CoV-2. Thus, there are likely additional animal species that serve as incidental hosts for SARS-CoV-2 and present a risk for establishment of new animal reservoirs in North America, as well as the emergence of new potential variants. We have identified candidate species at the Huanan market that may have been intermediate hosts involved in initial zoonotic spillover and North American animal species that present a high risk for SARS-CoV-2 zooanthroponosis. We generated expression constructs of these species’ ACE2 orthologs for testing susceptibility to infection with different SARS-CoV-2 variants, including the ancestral Wuhan-1 strain, D614G, and the five variants of concern (VOCs). We have further developed an analytical pipeline for assessing host susceptibility based on host transcriptomic data, using environmental sequence data obtained from the Huanan market to identify cross-species host signatures of infection. Susceptible species will be prioritized for downstream permissivity, surveillance, evolution, and pathogenesis studies, with the ultimate goal of assessing risk and deploying countermeasures such as vaccination at the human-animal interface. This work is also being expanded to study potential reservoirs for other emerging viruses such as MERS-CoV and mpox (monkeypox) virus, including in field studies and pathogenesis models to assess zoonotic risk and pandemic potential.

世 話 人 ： 〇 佐藤　佳（システムウイルス学分野）　 石井　健（ワクチン科学分野）

16:00 — 17:00２号館大会議室 Building. 2 Main Conference Room, The Institute of Medical Science

Ralph S. Baric

University of North Carolina at Chapel Hill・Professor

Models and Insights into Long COVID
Acute COVID19 infection may lead to acute respiratory disease syndrome and death and survivors may recover completely or progress to a variety of chronic disease states termed "Long COVID".  The genetic and molecular mechanisms governing differential outcomes remains unclear. The most prominent forms of long COVID include chronic inflammatory diseases of the lung and brain, which can present as breathing difficulties or cognitive disorders.  The presentation describes models of chronic lung inflammatory and brain phenotypes following infection of wildtype and genetic reference populations. Molecular and inflammatory phenotypes were used to provide insights into the molecular and genetic basis of disease.  Our data provide a series of animal models to study the progression from acute to chronic disease and support a model where dysregulated epithelial-immune cell interaction networks that promote chronic inflammatory and reparative defects in the lung.

世 話 人 ： 〇 佐藤　佳（システムウイルス学分野）　小檜山　康司（ワクチン科学分野）　　　　　　　　　　　　　　　　　　　　　　

概要： Parasites have developed a variety of physiological functions necessary for their survival within the specialized environment of the host. Using metabolic systems that are very different from those of the host, they can adapt to low oxygen tension present within the host animals. Most parasites do not use the oxygen available within the host to generate ATP even they reside oxygen rich circumstance such as blood, but rather employ systems anaerobic metabolic pathways. In addition, all parasites have a life cycle. In many cases, the parasite employs aerobic metabolism during their free-living stage outside the host. In such systems, parasite mitochondria play diverse roles. In particular, dynamic changes in the morphology and components of the mitochondria during the life cycle are very interesting elements of biological processes such as developmental control and environmental adaptation. As mitochondrial function is essential for the survival of the parasites, it should be promising target of chemotherapy. Anti-malarial atovaquone, which targets cytochrome b of parasite mitochondrial respiratory chain, is a well known example.

 In this talk, uniqueness of parasite respiratory chains and discovery of anti-COVID-19 candidate as well as anti-malarial compound, 5-aminolevulinic acid (5-ALA) will be presented.