S5E3: Can physics help combat COVID-19?

Numerous medical professionals, biologists and other experts have been combating COVID-19 and the havoc it has wrought since the pandemic began. Physicists have also joined the fray, including one from the University of Maine. The invention of a new microscope allows Sam Hess, a professor of physics at UMaine, to obtain new insight into the structure of the virus that causes COVID-19 — SARS-COV-2 — and the influenza virus. These findings could help pave the way for effective treatments. In this episode of “The Maine Question,” Hess discusses the development of this breakthrough in microscope technology and his decades-long quest to aid in the fight against these deadly diseases

MRI: ID-Development of a Hybrid Scanning Fluorescence and Sum Frequency Spectroscopy Imaging Microscope

With this award from the Major Research Instrumentation program (MRI), Michael Mason and colleagues from the Department of Chemistry at the University of Maine will develop a hybrid scanning fluorescence (FL) and sum frequency (SF) spectroscopy imaging microscope. The instrument will be constructed by the addition of sample scanning and FL capability to an existing broadband SF spectrometer. The SF NIR pump source will be used to excite SF at the sample interface, while a modulated Argon ion CW laser will excite FL. These collinear sources will give rise to spatially and temporally correlated SF and FL signals which will be separated and individually detected. The instrument will simultaneously measure the fluorescence and sum frequency to yield information about the localized dynamics of a single particle, i.e. protein, and spatially correlated structural information about the bulk material containing the particle. This yields information about the interaction between the particle and the bulk not accessible by any other method. The proposal will initially investigate test projects including the study of membrane domain structure and membrane-membrane interactions, e,g., correlation of the structure and dynamics of lipid and protein molecules within planar supported lipid bilayers. Successful development of this instrument could lead to major breakthroughs in several fields ranging from surface chemistry and biophysics to nanotechnology and cellular biology

Quantitative electron microscopy and fluorescence spectroscopy of the membrane distribution of influenza hemagglutinin

Although lipid-dependent protein clustering in biomembranes mediates numerous functions, there is little consensus among membrane models on cluster organization or size. Here, we use influenza viral envelope protein hemagglutinin (HA0) to test the hypothesis that clustering results from proteins partitioning into preexisting, fluid-ordered “raft” domains, wherein they have a random distribution. Japan HA0 expressed in fibroblasts was visualized by electron microscopy using immunogold labeling and probed by fluorescence resonance energy transfer (FRET). Labeled HA coincided with electron-dense, often noncircular membrane patches. Poisson and K-test (Ripley, B.D. 1977. J. R. Stat. Soc. Ser. B. 39:172–212) analyses reveal clustering on accessible length scales (20–900 nm). Membrane treatments with methyl-β-cyclodextrin and glycosphingolipid synthesis inhibitors did not abolish clusters but did alter their pattern, especially at the shortest lengths, as was corroborated by changes in FRET efficiency. The magnitude and density dependence of the measured FRET efficiency also indicated a nonrandom distribution on molecular length scales (∼6–7 nm). This work rules out the tested hypothesis for HA over the accessible length scales, yet shows clearly how the spatial distribution of HA depends on lipid composition

MRI: Acquisition of a SQUID Magnetometer for Analysis of Advanced Materials

Technical Summary: Superconducting quantum interference device (SQUID) magnetometry is a non-destructive technique that reveals detailed information about the electron spin interactions in many types of materials. This project will involve a state-of-the-art SQUID magnetometer and Magnetic Property Measurement System (MPMS), which is a critical tool for characterizing several types of materials currently being investigated by researchers within the Laboratory for Surface Science & Technology (LASST) and other University of Maine (UMaine) laboratories. Specific measurement capabilities include DC and AC magnetic susceptibility, magnetoresistivity, van der Paaw conductivity, and Hall mobility. State-of-the-art MPMS capabilities will be especially valuable to several research programs at UMaine pertaining to (i) surface magnetism in nanoparticles, (ii) magnetic anisotropies in sedimentary rocks, (iii) electrical transport in physical and chemical sensing devices, (iv) optical properties of nanostructures in high magnetic fields, and (v) magnetic nanoparticle based biosensors. The MPMS will serve as a focal point for training undergraduates, graduate students, postdocs, and visiting scientists in magnetic materials, nanotechnology, biophysics, and materials science. This instrument is a critical tool for expanding the capacity of UMaine research into magnetic aspects of nanotechnology, biophysics, sensor technology, and materials science. As no SQUID magnetometer currently exists in the State of Maine, the instrumentation will provide access for research projects from interested parties throughout the state, including non-Ph.D. granting institutions and small Maine businesses. The instrument is relatively easy to operate and provides direct information on electron spin interactions, and thus it will be a powerful tool to teach physics and nanotechnology concepts to several different constituents participating in UMaine outreach activities, including K-12 students and teachers, the general public, under-represented groups, and industry partners.Layman Summary: Superconducting quantum interference device (SQUID) magnetometry is a non-destructive technique that reveals detailed information about the electron spin interactions in many types of materials. Knowledge of electron interactions in materials is extremely important in building the next generation of computers, electronics, and contrast agents in biological magnetic screening techniques (i.e. MRI). To gain the necessary information, a system with control over both the magnetic field strength and temperature is critical. To this end, a SQUID/Magnetic Property Measurement System (MPMS) is ideal for these measurements. This project will purchase a state-of-the-art MPMS system and will be especially valuable to several research programs at UMaine pertaining to surface magnetism in nanoparticles, magnetic anisotropies in sedimentary rocks, electrical transport in physical and chemical sensing devices, and magnetic nanoparticle based biosensors. The proposed MPMS will serve as a focal point for training undergraduates, graduate students, postdocs, and visiting scientists in magnetic materials, nanotechnology, biophysics, and materials science. As no SQUID magnetometer currently exists in the State of Maine, the instrumentation will provide access for research projects from interested parties throughout the state, including non-Ph.D. granting institutions and small Maine businesses. The instrument is relatively easy to operate and provides direct information on electron spin interactions, and thus it will be a powerful tool to teach physics and nanotechnology concepts to several different constituents participating in UMaine outreach activities, including K-12 students and teachers, the general public, under-represented groups, and industry partners

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN

The Spread of Fecally Transmitted Parasites in Socially-Structured Populations

Mammals are infected by a wide array of gastrointestinal parasites, including parasites that also infect humans and domesticated animals. Many of these parasites are acquired through contact with infectious stages present in soil, feces or vegetation, suggesting that ranging behavior will have a major impact on their spread. We developed an individual-based spatial simulation model to investigate how range use intensity, home range overlap, and defecation rate impact the spread of fecally transmitted parasites in a population composed of social groups (i.e., a socially structured population). We also investigated the effects of epidemiological parameters involving host and parasite mortality rates, transmissibility, disease–related mortality, and group size. The model was spatially explicit and involved the spillover of a gastrointestinal parasite from a reservoir population along the edge of a simulated reserve, which was designed to mimic the introduction pathogens into protected areas. Animals ranged randomly within a “core” area, with biased movement toward the range center when outside the core. We systematically varied model parameters using a Latin hypercube sampling design. Analyses of simulation output revealed a strong positive association between range use intensity and the prevalence of infection. Moreover, the effects of range use intensity were similar in magnitude to effects of group size, mortality rates, and the per-contact probability of transmission. Defecation rate covaried positively with gastrointestinal parasite prevalence. Greater home range overlap had no positive effects on prevalence, with a smaller core resulting in less range overlap yet more intensive use of the home range and higher prevalence. Collectively, our results reveal that parasites with fecal-oral transmission spread effectively in socially structured populations. Future application should focus on parameterizing the model with empirically derived ranging behavior for different species or populations and data on transmission characteristics of different infectious organisms

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts