Please feel free to browse through brief writing samples.

Recently published short news reports are available at these links:

Hematology Advisor: https://www.hematologyadvisor.com/author/vicki-moore-phd/

Oncology Nurse Advisor: https://www.oncologynurseadvisor.com/author/vicki-moore-phd/

Older writing samples:

Bacteria Designed to Provide a Biomarker of Gut Inflammation

by Vicki Moore, PhD

A strain of E. coli has been developed to produce a detectable signal in the presence of gut inflammation in mice.

August 10, 2017 – A genetic circuit has been engineered into E. coli to provide a diagnostic signal of gut inflammation in mice, and this modification has been shown to persist for at least 6 months.

“Live, engineered bacteria can be used as non-invasive diagnostics to detect transient (or highly localized) molecules in the gut, or as therapeutics,” explained study author David T. Riglar, PhD, of Harvard Medical School and Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, and colleagues. The study was reported May 29, 2017, in Nature Biotechnology.

Inflammation in the gut is frequently associated with increased levels of reactive oxygen species, a product of which in some cases is the molecule tetrathionate. The study authors developed an inducible genetic system (named PAS638) in which β-galactosidase expression is driven by a tetrathionate-inducible promoter. This expression can be visualized through a colorimetric bacterial colony screening, with tetrathionate-activated expression leading to blue E. coli colonies. The researchers placed this genetic construct into the genomes of E. coli that were used to inoculate the guts of mice and then measured expression in E. coli from fecal samples. Verification was provided by mass spectrometric detection of tetrathionate in cecum extracts.

Inflammation was induced in mice by infection with a Salmonella typhimurium strain (Δttr strain) that lacked the ability to metabolize tetrathionate (n = 7). Controls were not infected (n = 7) or were infected with a version of S. typhimurium that kept metabolism of tetrathionate intact (n = 6). Colony counts from samples in each treatment group were recorded and verified using both the inflammation biomarker lipocalin-2 and histopathology of gut specimens.

After 4-5 days of infection, fecal samples from each group showed that β-galactosidase expression occurred with PAS638 only in mice infected with the S. typhimurium Δttr strain, and this expression correlated well with other signs of inflammation (P = .03). Mass spectrometry also showed tetrathionate was significantly more abundant in cecum extracts of S. typhimurium Δttr-infected versus uninfected mice (P < .0001) at a low micromolar concentration (extrapolated to cecum volume). Finally, observation of E. coli colonies representing induction of PAS638 showed that this genetic system in mice persisted for six months of study.

Use of this genetic system as a diagnostic marker seemed sensitive to the specific day of measurement post-infection. However, this appeared to simply be a result of the expression system requiring a minimum threshold level of tetrathionate to be present.

While synthetic genetic circuits are often vulnerable to mutations when introduced into a host organism, the fact that this genetic system remained unchanged and functional for an entire 6-month period suggests that this is a promising technique.

“In conclusion, we show that synthetic bacterial devices can colonize the complex host mammalian gut and be used to monitor and analyze the course of a disease over an extended timeframe,” stated the study authors.

This study was supported by a grant from the National Institutes of Health, and the authors report no competing financial interests.

Report based on the following reference: Riglar DT, Giessen TW, Baym M, et al. Engineered bacteria can function in the mammalian gut long-term as live diagnostics of inflammation. Nat Biotechnol. 2017;35:653-658.

Metabolite from a Gut Bacterium Helps Protect Against Influenza

by Vicki Moore, PhD

Gut desaminotyrosine protects against influenza in mice.

August 10, 2017 – Desaminotyrosine (DAT), a metabolite from a gut microbe, exhibits activity that protects against influenza infection.

“Our findings that preexisting members of the human microbiota protect the host from influenza infection may have implications for the known heterogeneous response to this infection in humans,” stated Ashley Steed, MD, PhD, from Washington University School of Medicine, in St. Louis, Missouri, and colleagues. Results were reported in Science on August 4, 2017.

Based on evidence that type I interferon (IFN) forms an important component in the immune response to infection, as well as evidence that the gut microbiome influences immune function, the researchers set out to investigate the effects of gut metabolites on host IFN activity.

Mice were developed that showed varying levels of type I IFN activity either through enhancement or knockout of components of this signaling pathway. IFN activity was measured through a varicella zoster-specific bioassay, and through both quantitative real-time polymerase chain reaction and sequencing of RNA.

Mice with more type I IFN activity showed better viability upon influenza infection (n = 18-40 per treatment group in five experiments; P < .0001), indicating that type I IFN activity is strongly protective against influenza.

Of 84 gut metabolites initially screened for association with IFN activity, DAT, a product of flavonoid and amino acid metabolism, emerged as a leading candidate. Treatment with DAT led to significantly increased RNA content in lungs for genes related to IFN-signaling (n = 5 mice per group in two experiments; P < .05 or < .01, depending on the gene).

While viral load at 5 days post-infection was not influenced by presence of DAT, treatment with DAT led to significantly less influenza RNA in the lungs (n = 10 mice per group in two experiments; P < .01). Tissue and airway analyses indicated that DAT was associated with less damage to the lungs by influenza and that the protective effects of DAT were greatest with pretreatment during the week before influenza infection.

Further analysis suggested that DAT exerts its influence on type I IFN activity likely through amplification rather than induction. Additionally, investigation of gut microbiota suggested that Clostridium orbiscindens is the primary source of DAT in the mouse gut. Whether and how other gut metabolites influence DAT metabolism is still a mystery, though this study illustrates a plausible route by which the gut microbiome may influence immune response.

Ultimately, results of this study “suggest that prior colonization by specific bacteria and a flavonoid enriched diet are key components that modulate the immune response to influenza infection,” the authors concluded.

This study was supported by the National Institutes of Health in addition to other sources of funding. Authors’ disclosures are available with the article.

Report based on the following reference: Steed AL, Christophi GP, Kaiko GE, et al. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. Science 2017;357:498-502.

Zika Vaccine Can Protect Against Congenital Effects in Utero

In mice infected with Zika virus, vaccination reduces fetal damage.

by Vicki Moore, PhD

July 31, 2017 – Vaccination against Zika virus (ZIKV) in mice shows strong potential to limit fetal damage, according to a recent study evaluating two types of vaccines against the virus.

“Collectively, the virological and histopathological data suggest that immunization with prM-E mRNA LNP or ZIKV-NS1-LAV vaccines can reduce dissemination of ZIKV to the placenta, which substantially decreases the likelihood of placental infection and injury; this prevents vertical transmission and improves fetal outcome,” stated study author Dr. Michael Diamond of the Washington University School of Medicine in St. Louis, Missouri, and colleagues. Findings of this study were reported July 13, 2017, in Cell.

Many Zika vaccine studies have shown protection against the virus in multiple animal models, but, prior to this study, none had been evaluated for protection of fetuses.

This study’s authors tested two types of vaccines in mice, one a pre-existing mRNA-based vaccine against the virus’s prM-E subunit (prM-E mRNA LNP), and the other a new live-attenuated vaccine (ZIKV-NS1-LAV) that included mutations in the NS1 gene that interfere with N-glycosylation. Female mice were immunized with either vaccine or given a placebo and then infected with Zika, followed by mating with males. Maternal and fetal samples were evaluated for viral loads, appearance, viability, and other factors.

Both vaccine types appeared to protect fetuses and placentas against Zika virus. For the prM-E mRNA LNP vaccine treatment, 100% of fetuses in the placebo group were resorbed (N = 17), while 100% of the fetuses in the vaccine group were born (N = 14; P < .0001). About 90% of the fetuses (N = 48) harvested from ZIKV-NS1-LAV vaccine-treated mothers appeared viable at 13 days, while about 70% of the fetuses (N = 32) from placebo-treated mothers in this group were viable at that time (P < .05).

Mice in the ZIKV-NS1-LAV treatment group showed significantly reduced levels of viral RNA in both the placenta (276,000-fold reduction) and fetal heads (20,000-fold reduction) versus RNA levels in tissues from the placebo group. Viral RNA from this vaccine treatment group was often present below the limit of detection, suggesting the virus likely had a very low rate of transmission to young in this group.

According to the authors, a comparison of the two vaccine types with each other was limited by different procedures applied to each treatment group. However, the strong response seen with prM-E mRNA LNP vaccine suggests substantial efficacy for this vaccine in protecting fetuses. “Where safety concerns are greatest (e.g., females during childbearing years, immunocompromised, and those with certain co-morbidities), the non-replicating prM-E mRNA LNP subunit-based vaccine may have greatest utility and shortest pathway to licensure,” the study authors noted.

This study was supported by grants from the National Institutes of Health, among other sources. Authors’ disclosures are available with the article.

Report based on the following reference: Richner JM, Jagger BW, Shan C, et al. Vaccine mediated protection against Zika virus-induced congenital disease. Cell. 2017;170:272-283.