A5023388501- Evolution and Genetic Dynamics
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Mosquito-borne diseases and control
- Peptidase Inhibition and Analysis
- Plant Virus Research Studies
- Genomics and Phylogenetic Studies
- Neuropeptides and Animal Physiology
- Insect symbiosis and bacterial influences
- Influenza Virus Research Studies
- Bacteriophages and microbial interactions
- Molecular Biology Techniques and Applications
- Viral gastroenteritis research and epidemiology
- Mycobacterium research and diagnosis
- Hepatitis C virus research
- Mathematical and Theoretical Epidemiology and Ecology Models
- CRISPR and Genetic Engineering
- COVID-19 Clinical Research Studies
- Viral Infections and Vectors
- Rabies epidemiology and control
- Animal Behavior and Reproduction
- Genetic diversity and population structure
- Evolutionary Game Theory and Cooperation
- Malaria Research and Control
- Pneumonia and Respiratory Infections
Swift Engineering (United States)
2019
University of Michigan
2018
University of North Carolina at Chapel Hill
2014-2017
University of Arizona
2014
ABSTRACT Human dipeptidyl peptidase 4 (hDPP4) was recently identified as the receptor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection, suggesting that other mammalian DPP4 orthologs may also support infection. We demonstrate mouse cannot MERS-CoV However, employing a scaffold, we two critical amino acids (A288L and T330R) regulate species specificity in mouse. This knowledge can rational design of mouse-adapted rapid assessment therapeutics.
ABSTRACT Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as significant human pathogen. In 2015, ZIKV was detected Brazil, the resulting epidemic spread throughout Western Hemisphere. Severe complications from infection include neurological disorders such Guillain-Barré syndrome adults variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, demise. There is an urgent need for tools...
Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. Mouse DPP4 (mDPP4) does not support MERS-CoV entry; however, changes at positions 288 and 330 can confer permissivity. Position the charge glycosylation state of mDPP4. We show that is a major factor impacting receptor function. These results provide insight into species-specific differences host range may inform mouse model development.
Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several orthologs, including mouse, ferret, hamster, guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse plays a role in blocking infection. Here, we tested whether also acts determinant permissivity for DPP4. We found that, while important these additional sequence structural determinants...
ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis arthralgia over the past decade. These include recent outbreak in Caribbean islands Americas that caused more than 1 million cases viral arthralgia. Despite major impact CHIKV on global health, determinants promote CHIKV-induced disease are incompletely understood. Most strains contain conserved opal stop codon at end nsP3 gene. However,...
Abstract Sex is ubiquitous in the natural world, but nature of its benefits remains controversial. Previous studies have suggested that a major advantage sex ability to eliminate interference between selection on linked mutations, phenomenon known as Hill–Robertson interference. However, those may missed both important advantages and disadvantages sexual reproduction because they did not allow distributions mutational effects interactions (i.e., genetic architecture) evolve. Here we...
Viruses evolve rapidly, providing a unique system for understanding the processes that influence rates of molecular evolution. Neutral theory posits evolutionary rate increases linearly with mutation rate. The occurrence deleterious mutations causes this relationship to break down at high rates. Previous studies have identified as an important phenomenon, particularly RNA viruses which can mutate near extinction threshold. We propose in addition dynamics, viral within-host dynamics also...
The existence of complex (multiple-step) genetic adaptations that are "irreducible" (i.e., all partial combinations less fit than the original genotype) is one longest standing problems in evolutionary biology. In standard genetics parlance, these require crossing a wide adaptive valley deleterious intermediate stages. Here we demonstrate, using simple model, evolution can cross valleys to produce "irreducibly complex" by making use previously cryptic mutations. When revealed an capacitor,...
Most of our knowledge dominance stems from studies deleterious mutations. From these we know that most mutations are recessive, and this recessivity arises a hyperbolic relationship between protein function (i.e., concentration or activity) fitness. Here investigate whether can be used to make predictions about the beneficial in single gene. We employed model system – bacteriophage φ6 allowed us generate collection haploid conditions so it was not biased toward either dominant recessive...
Abstract The human microbiome has been studied in the context of a number diseases and recently gaining momentum field cancer research. composition gut microbiome, for example, shown to affect progression may act as both biomarker therapeutic target. Metagenomic shotgun sequencing played large role characterizing microbial communities. However, direct multiple complex samples parallel relatively low sensitivity struggles accurately characterize microbiome. Alternatively, targeted PCR can be...
The human microbiome has been studied in the context of a number diseases and recently gaining momentum field cancer research. composition gut microbiome, for example, shown to affect progression may act as both biomarker therapeutic target. Metagenomic shotgun sequencing played large role characterizing microbial communities. However, direct multiple complex samples parallel relatively low sensitivity struggles accurately characterize microbiome. Alternatively, targeted PCR can be used...