Biology subjects

Amundson, K.

Publications and source records attributed to Amundson, K..

4 recordsLinked to original sources

bioRxiv2024

CD388: A universally protective Drug-Fc Conjugate that targets influenza virus neuraminidase

The ability of the influenza virus to elude humoral immunity by rapid antigenic shift presents a sustained and urgent threat to human health. Globally, seasonal influenza causes an estimated 3 - 5 million cases of severe disease and 300,000 - 500,000 deaths annually, with increased potential for mortality during pandemics1. The recent outbreaks of avian H5N1 in bird populations, subsequent spread to cattle and appearance in humans, highlight the need for effective broad-spectrum influenza antivirals for treatment, prophylaxis and pandemic preparedness. The narrow, strain-specific immunity induced by current seasonal vaccines and mismatches between vaccine strains and circulating viruses result in limited vaccine effectiveness (VE) rates2. Furthermore, VE is even lower in immune-compromised and - senescent populations3. Strategies that provide durable, universal influenza protection in healthy and high-risk populations are urgently needed. Here, we describe CD388, a first-in-class antiviral drug-Fc conjugate (DFC) in clinical trials for seasonal influenza prevention (NCT05285137 and NCT05523089). CD388 comprises a multivalent small molecule inhibitor of influenza virus neuraminidase (NA) linked to a CH1-Fc hybrid domain of human IgG1 engineered for extended half-life. CD388 demonstrated potent, universal activity across influenza A and B viruses, including high pathogenicity and NA resistant strains, a low potential for resistance development, and efficacy in lethal mouse infection models. CD388 is the first therapeutic with the potential for universal prevention of influenza A and B in healthy and high-risk populations.

microbiology↗

bioRxiv2023

A K-mer based Bulked Segregant Analysis approach to map seed traits in unphased heterozygous potato genomes

High-throughput sequencing-based methods for bulked segregant analysis (BSA) allow for the rapid identification of genetic markers associated with traits of interest. BSA studies have successfully identified qualitative (binary) and quantitative trait loci using QTL mapping. However, most traditional QTL mapping approaches require a reference genome. Here, we combine high throughput short read sequencing with bulk segregant analysis of k-mers (BSA-k-mer). This method can be applied to any organism and is particularly useful for species with genomes too different from the closest sequenced genome. It is also instrumental when dealing with highly heterozygous and polyploid genomes without phased haplotype assemblies and for which a single haplotype can control a trait. Finally, it is flexible in terms of population structure. Here, we present the application of the BSA-k-mer method for the rapid identification of candidate regions related to seed spot and seed size in diploid potato. While conventional QTL mapping of parental genotypes did not generate any signal, candidate loci were identified for each trait using the BSA-k-mer approach. The seed spot loci match with previously identified loci associated with pigmentation in potato. The loci associated with seed size are novel. Both sets of loci are potentially instrumental in future breeding towards true seeds in potato. Article SummaryIdentifying genes linked to agronomic traits in potatoes is challenging because potato genomes are complex and variable. We are investigating the genetic basis of seed size and color. Seeds were categorized as large or small, or spotted or not, based on simple visual observation. Next, DNA sequences from each individual were mined for association between random short sequences (k-mers) and those two traits. This more flexible method allowed us to identify regions of the potato genome associated with both traits.

plant biology↗

bioRxiv2023

Polymer biodegradation by Halanaerobium promotes reservoir souring during hydraulic fracturing.

Hydraulically fractured shale reservoirs have facilitated studies of unexplored niches in the continental deep biosphere. Members of the genus Halanaerobium are ubiquitous in these environments. Polymers like guar gum used as gelling agents in hydraulic fracturing fluids are known to be fermentable substrates, but metabolic pathways encoding these processes have not been characterized. To explore this, produced water samples from the Permian Basin were incubated at 30{degrees}C to simulate above-ground storage conditions, and at 60{degrees}C to simulate subsurface reservoir conditions. Guar metabolism coincided with Halanaerobium enrichment only at 30{degrees}C, revealing genes for polymer biodegradation through the mixed-acid fermentation pathway in different metagenome-assembled genomes (MAGs). Whereas thiosulfate reduction to sulfide is often invoked to explain the dominance of Halanaerobium in these settings, Halanaerobium genomes did not uncover genes for this metabolism. Sulfide production was observed in 60{degrees}C incubations, with corresponding enrichment of Desulfohalobium and Desulfovibrionaceae that possess complete pathways for coupling mannose and acetate oxidation to sulfate reduction. These findings outline how production of fermentation intermediates (mannose, acetate) by Halanaerobium in topside settings can result in reservoir souring when these metabolites are introduced into the subsurface through produced water re-use. ImportanceHydraulically fractured shale oil reservoirs are ideal for studying extremophiles such as thermohalophiles. During hydraulic fracturing, reservoir production water is stored in surface ponds prior to re-use. Microorganisms in these systems therefore need to withstand various environmental changes such as the swing between warm downhole oil reservoir temperatures and cooler surface conditions. This study follows this water cycle during fracking and the associated microbial metabolic potential. Of particular interest are members of the genus Halanaerobium, that have been reported to reduce thiosulfate contributing to souring of oil reservoirs. Here, we show that some Halanaerobium strains were unable to grow under oil reservoir temperatures and do not possess genes for thiosulfate reduction. Rather, it is likely that these organisms metabolize complex organics in fracking fluids at lower temperatures, thereby generating substrates that support reservoir souring by thermophilic sulfate-reducing bacteria at higher temperatures.

microbiology↗

bioRxiv2019

Genomic Outcomes of Haploid Induction Crosses in Potato (Solanum tuberosum L.)

The challenges of breeding autotetraploid potato (Solanum tuberosum) have motivated the development of alternative breeding strategies. A common approach is to obtain uniparental dihaploids from a tetraploid of interest through pollination with S. tuberosum Andigenum Group (formerly S. phureja) cultivars. The mechanism underlying haploid formation of these crosses is unclear, and questions regarding the frequency of paternal DNA transmission remain. Previous reports described aneuploid and euploid progeny, which, in some cases, displayed genetic markers from the haploid inducer. Here, we surveyed a population of 167 presumed dihaploids for large-scale structural variation that would underlie chromosomal addition from the haploid inducer, and for small-scale introgression of genetic markers. In 19 progeny, we detected ten of the twelve possible trisomies and, in all cases, demonstrated the non-inducer parent origin of the additional chromosome. Deep sequencing indicated that occasional, short-tract signals appearing of haploid inducer origin were better explained as technical artifacts. Leveraging recurring CNV patterns, we documented sub-chromosomal dosage variation indicating segregation of polymorphic maternal haplotypes. Collectively, 52% of assayed chromosomal loci were classified as dosage variable. Our findings help elucidate the genomic consequences of potato haploid induction and suggest that most potato dihaploids will be free of residual pollinator DNA.

genomics↗