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Biology subjects

Pedersen, T.

Publications and source records attributed to Pedersen, T..

4 recordsLinked to original sources

Defined Mars Media (DMM), a chemically defined simulant of the soluble macro- and micro- nutrients in Mars regolith for use in biological research

Mars harsh yet workable surface conditions, such as manageable temperatures, availability of solar energy, and in situ resources like water ice, carbon dioxide, and mineral-rich regolith, make it a compelling target for supporting life beyond Earth. However, existing experiments testing chemical habitability in Mars conditions generally rely on leachates of physical regolith simulants, which vary in composition across simulant types, leaching conditions, and production batches. We introduce a defined Mars media (DMM) that accurately simulates the biologically relevant nutrients (nitrogen, phosphorus, and sulfur) and stressors (perchlorates, heavy metals) in Martian regolith when it is leached in water at neutral pH. We formulated DMM by combining direct rover and lander measurements from Mars with laboratory measurements of regolith simulant leachates. We validate DMM from a 1x to 20x concentrate, equivalent to 40 g/L to 800 g/L of leached regolith. Using DMM with acetate as a Mars atmosphere-derived carbon source, we grew eight bacteria, demonstrating that organisms can source all essential nutrients from Martian resources. We also demonstrate that microbial growth in DMM is robust to uncertainties in Martian regolith composition: sensitivity experiments can identify limiting trace element nutrients and toxins in DMM, and show that bacterial growth is maintained across at least an order of magnitude variation in their concentrations. This is the first defined Mars regolith media recipe containing both macro- and micro-nutrients, and designed specifically for biological experimentation. By shifting from variable leachate-based approaches to a defined aqueous analog, we enable controlled hypothesis testing of microbial survival, growth, and function in a Martian chemical environment. DMM will enable further research on astrobiology, biological in situ resource utilization, large-scale soil remediation, and terraforming. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/719001v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@37408forg.highwire.dtl.DTLVardef@16fabfforg.highwire.dtl.DTLVardef@84fa43org.highwire.dtl.DTLVardef@4a7c5e_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

BioBloom, a method for barcoded saturation mutagenesis of an entire bacterial genome

Saturation mutagenesis is a powerful tool for understanding and engineering the function of biological systems. and has been applied successfully to characterize the mutational landscape of individual proteins and genetic loci. However. it has not been applied at the whole-genome scale due to the challenges of both creating and quantifying a saturating set of mutations. Here we introduce BioBloom. a retron-based method for barcoded saturation mutagenesis at the scale of a whole bacterial genome. We constructed a barcoded BioBloom library with >99% projected sampling of saturating single - nucleotide polymorphism (SNP) mutations of the E. coli genome, and applied it to identify beneficial mutations under salt and antibiotic selection. Relative to other techniques like CRISPR-enabled mutagenesis or Adaptive Laboratory Evolution, BioBloom excels at identifying diverse causal SNPs quickly and at smaller working volumes. A barcoded, saturating mutation library is also a shared resource, and we are releasing the updated BioBloom-Ec.-2.0 library to the scientific community for broader adoption and application. Together. BioBloom makes barcoded saturation mutagenesis accessible at whole-genome scale, creating new opportunities for large-scale data collection and bacterial engineering.

microbiology↗

Blood-based targeted metabolipidomics reveals altered omega fatty acid-derived lipid mediators in relapsing-remitting multiple sclerosis patients

Unresolved and uncontrolled inflammation is considered a hallmark of pathogenesis in chronic inflammatory diseases like multiple sclerosis (MS), suggesting a defective resolution process. Inflammatory resolution is an active process partially mediated by endogenous metabolites of dietary polyunsaturated fatty acids (PUFA), collectively termed specialized pro-resolving lipid mediators (SPMs). Altered levels of resolution mediators have been reported in several inflammatory diseases and may partly explain impaired inflammatory resolution. Performing LC-MS/MS-based targeted lipid mediator profiling, we observed distinct changes in fatty acid metabolites in serum from 30 relapsing-remitting MS (RRMS) patients relative to 30 matched healthy subjects (HS). Robust linear regression revealed 12 altered lipid mediators after adjusting for confounders (p <0.05). Of these, 15d-PGJ2, PGE3, and LTB5 were increased in MS while PGF2a, 8,9-DiHETrE, 5,6-DiHETrE, 20-HETE, 15-HETE, 12-HETE, 12-HEPE, 14-HDoHE, and DHEA were decreased in MS compared to HS. In addition, 12,13-DiHOME and 12,13-DiHODE were positively correlated with expanded disability status scale values (EDSS). Using Partial Least Squares, we identified several lipid mediators with high VIP scores (VIP > 1: 32% - 52%) of which POEA, PGE3, DHEA, LTB5, and 12-HETE were top predictors for distinguishing between RRMS and HS (AUC =0.75) based on the XGBoost Classifier algorithm. Collectively, these findings suggest an imbalance between inflammation and resolution. Altogether, lipid mediators appear to have potential as diagnostic and prognostic biomarkers for RRMS.

biochemistry↗

Life history genomic regions explain differences in Atlantic salmon marine diet specialization

O_LIAnimals employ various foraging strategies along their ontogeny to acquire energy, and with varying degree of efficiencies, to support growth, maturation and subsequent reproduction events. Individuals that can efficiently acquire energy early are more likely to mature at an earlier age, as a result of faster energy gain which can fuel maturation and reproduction. C_LIO_LIWe aimed to test the hypothesis that heritable resource acquisition variation that co-varies with efficiency along the ontogeny would influence maturation timing of individuals. C_LIO_LITo test this hypothesis, we utilized Atlantic salmon as a model which exhibit a simple, hence trackable, genetic control of maturation age. We then monitored the variation in diet acquisition (quantified as the stomach fullness and composition) of individuals with different ages, and linked it genomic regions (haploblocks) that were previously identified to be associated with age-at-maturity. C_LIO_LIConsistent with the hypothesis, we demonstrated that one of the life history genomic regions tested (six6) was indeed associated with age-dependent differences in stomach fullness. Prey composition was marginally linked to both genomic regions (six6 and vgll3). We further showed Atlantic salmon switched to the so-called "feast and famine" strategy along the ontogeny, where older age groups exhibited heavier stomach content, but that came at the expense of running on empty more often. C_LIO_LIThese results suggest genetic variation underlying resource utilization variation may explain the genetic basis of age structure in Atlantic salmon. Given that ontogenetic diet has a genetic component and the strong spatial diversity associated with these genomic regions, we predict populations with diverse maturation age will have diverse evolutionary responses to future changes in marine food-web structures. C_LI

ecology↗