Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that was first reported in Wuhan, China in December of 2019 and has since caused a global pandemic resulting in millions of deaths and tens of millions of patients testing positive for infection. Analysis of different viral strains has identified a D614G change in the spike protein that is correlated with the virus becoming more transmissible. While studies have shown G614 viruses to be more transmissible, the effects of this mutation on the host response, especially on the cellular level, are yet to be fully elucidated. In this experiment we infected NHBE cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at three different time points to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes, enriched Gene Ontology terms and dysregulated signaling pathways. We detected over 2,000 differentially expressed genes, over 600 Gene Ontology terms, and 29 affected pathways between the two treatments. Many of these entities play a role in immune signaling and response. When comparing the different strains and different time points we found more overall similarities between matched time points than across different time points with the same strain. When specifically comparing the affected pathways, we saw that the 24hr time point of the New York strain was more similar to the 12hr time point of the Washington strain with a large number of pathways related to translation being inhibited in both strains at these time points. These results suggest that D614G substitution in the spike protein, combined with other nonsynonymous changes in the viral gene products cause distinct responses in infected host cells, especially relating to how quickly translation is dysregulated after infection. These observed differences in the intracellular host response to infection could play a role in driving the increase in pathogenicity and mortality seen in the New York outbreaks versus the Washington outbreaks at the beginning of the SARS-CoV-2 pandemic.
Project description:Sex specificity of the C. elegans metabolome
Russell N. Burkhardt1, Alexander B. Artyukhin1,3, Erin Z. Aprison2, Brian J. Curtis1, Bennett W. Fox1, Andreas H. Ludewig1, Amaresh Chaturbedi4, Oishika Panda1, Chester J. J. Wrobel1, Siu S. Lee4, Ilya Ruvinsky2, and Frank C. Schroeder1,
1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States
2Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, United States
3Current address: Chemistry Department, College of Environmental Science and Forestry, State University of New York, Syracuse, New York 13210, United States
4Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, United States
Correspondence to fs31@cornell.edu
Project description:Sex specificity of the C. elegans metabolome
Russell N. Burkhardt1, Alexander B. Artyukhin1,3, Erin Z. Aprison2, Brian J. Curtis1, Bennett W. Fox1, Andreas H. Ludewig1, Amaresh Chaturbedi4, Oishika Panda1, Chester J. J. Wrobel1, Siu S. Lee4, Ilya Ruvinsky2, and Frank C. Schroeder1,
1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States
2Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, United States
3Current address: Chemistry Department, College of Environmental Science and Forestry, State University of New York, Syracuse, New York 13210, United States
4Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, United States
Correspondence to fs31@cornell.edu
Project description:Particulate matter (PM) exposure and metabolic syndrome (MetSyn) coexist in both industrialized and developing nations. PM and MetSyn are strong risk factors for chronic obstructive pulmonary disease (COPD) and asthma. After the World Trade Center collapse in 9/11/2001, PM-exposed individuals from the Fire Department of New York City (FDNY) developed a progressively lung disease. This nested case-cohort study is composed of never smoking, WTC exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. Representative cohort controls with serum drawn within six months of 9/11 (n=100). FEV1 at subspecialty exam defined cases: susceptible World Trade Center Lung Injury (WTC-LI) cases (n=50) had FEV1< lower limit of normal (LLN) and resistant WTC-LI cases with FEV1 ≥107% predicted (n=50). This study will determine the metabolomics profile that differentiates firefighters with WTC-LI, firefighters resistant to WTC-LI, and similarly exposed cohort controls.
Project description:Using an integrated systems approach, the expressed proteome of B. diazoefficiens strain 110scp4 was measured under i) normal, oxic growth, and ii) microoxic growth condtions. This included, as a first step, the sequencing and de novo assembly of the genome of this widely used rhizobial model strain, which turned out to harbor several deletions and insertions compared to the B. diazoefficiens USDA 110 NCBI reference genome. With this optimal basis in hand, a shotgun proteomics approach relying on a slightly adapated FASP protocol was carried out, allowing to identify 2900 (oxia) and 2826 (microoxia) proteins, respectively, thereby largely expanding the proteome known to be expressed under microoxic conditions.
Project description:Oligonucleotide catabolism-derived gluconucleosides in C. elegans
Brian J. Curtis, Tyler J. Schwertfeger, Russell N. Burkhardt, Bennett W. Fox, Jude Andrzejewski, Chester J. J. Wrobel, Jingfang Yu, Pedro R. Rodrigues, Arnaud Tauffenberger*, and Frank C. Schroeder*
Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.
Project description:During the summer of 2015, New York, New York, USA, had one of the largest and deadliest outbreaks of Legionnaires' disease in the history of the United States. A total of 138 cases and 16 deaths were linked to a single cooling tower in the South Bronx. Analysis of environmental samples and clinical isolates showed that sporadic cases of legionellosis before, during, and after the outbreak could be traced to a slowly evolving, single-ancestor strain. Detection of an ostensibly virulent Legionella strain endemic to the Bronx community suggests potential risk for future cases of legionellosis in the area. The genetic homogeneity of the Legionella population in this area might complicate investigations and interpretations of future outbreaks of Legionnaires' disease.