Biology subjects

Mardick, J. I.

Publications and source records attributed to Mardick, J. I..

3 recordsLinked to original sources

bioRxiv2026

Rapid Identification of Infections Directly from Isolates and Clinical Specimens with the MasSpec Pen Technology

The time-consuming nature of conventional bacterial identification methods, coupled with rising resistance to antibiotics, presents a serious challenge in the rapid diagnosis and treatment of patients suffering from severe infection and sepsis. In this study, we demonstrate that the MasSpec Pen (MSPen) technology enables rapid identification of the most frequently occurring bacterial species in human infections. A total of 755 clinical bacterial isolates prospectively collected from pediatric and adult patients were analyzed using the MSPen to create a library of molecular profiles. The mass spectra obtained presented distinct molecular patterns for bacterial species, with high relative abundances of bacterial metabolites and lipids, including unique quinolone signaling molecules in Pseudomonas aeruginosa, phosphoethanolamine (PE) lipids in Enterobacteriaceae, and phosphatidylglycerol (PG) lipids in Staphylococcus species. Logistic and multinomial lasso models using relative abundances or logarithmic-ratio abundance calculations achieved >95% accuracy for Gram stain typing and >92% for species-level identification in isolates. Random forest models yielded comparable performance, reinforcing the robustness of these findings across approaches. Many of the metabolite and lipid predictive features from each isolate classifier were detected when directly analyzing highly infected synovial fluid, tissue, pleural fluid, and breast aspirate specimens from patients. Notably, significant variations in the natural isotopic abundance of specific lipids were observed in infected patient samples, indicating presence of bacterial infection. This study demonstrates the potential of MSPen for the direct identification of bacterial-specific metabolites and lipids in clinical isolates and specimens, offering promise for future advancements in the MSPen technology for rapid bacterial identification. Teaser.MSPen shows potential for rapid, direct identification of bacterial metabolites and lipids, enabling accurate bacterial classification.

microbiology↗

bioRxiv2025

FGF-dependent, polarized SOS activity orchestrates directed migration of C. elegans muscle progenitors independently of canonical effectors in vivo

Directed cell migration is essential for animal development, tissue maintenance, regeneration, and disease states. Cells often migrate towards, or away from, sources of secreted signaling proteins that impart spatial information. How migrating cells interpret extracellular signals to orient and navigate within living animals is a fundamental question in biology. Receptor Tyrosine Kinase (RTK) signaling plays critical roles in cell migration, and aberrant RTK pathway activity is a key driver of multiple types of cancers. Yet, how RTKs control cell migration in living animals remains unclear, in part due to essential, pleiotropic roles of key proteins in development. To elucidate how RTK signaling controls cell migration in vivo, we dissected spatial and temporal requirements for key signal transduction and cytoskeletal regulatory proteins using C. elegans muscle progenitor migration as a tractable model. Cell type-specific depletion of endogenously tagged proteins revealed that homologs of FGFR, GRB2, SOS, and Ras control cell migration independently of their canonical ERK, PI3K, Akt, mTOR, and PLC{psi} effectors. Instead, we found that FGF-dependent, polarized SOS-1 orients migrating cells towards an FGF source, and mislocalizing SOS activity within migrating cells severely disrupts migration independent of ERK. Cell type-specific, gain-of-function experiments demonstrated that activated Ras is largely permissive for anterior migration in this context, and an intragenic revertant identified in a screen for suppressors of activated Ras/let-60 revealed that signal transduction in migrating muscle progenitors can be genetically uncoupled from Ras-ERK-dependent developmental processes. We found that conserved regulators of branched actin assembly control SM protrusive dynamics but are not essential for accurate, FGF-directed migration. Our findings provide a novel mechanism for RTK-directed cell migration in vivo and highlight the importance of cell type-specific approaches to elucidate signal transduction mechanisms in physiologically relevant contexts. Our work also outlines a comprehensive framework for investigating RTK-dependent processes in a multicellular organism and introduces a versatile genetic toolkit for dissecting spatial and temporal signaling dynamics fundamental to development, homeostasis, and disease.

cell biology↗

bioRxiv2021

Parallel Rap1>RalGEF>Ral and Ras signals sculpt the C. elegans nervous system

Ras is the most commonly mutated oncogene in humans and uses three oncogenic effectors: Raf, PI3K, and RalGEF activation of Ral. Understanding the importance of RalGEF>Ral signaling in cancer is hampered by the paucity of knowledge about their function in animal development, particularly in cell movements. We found that mutations that disrupt function of RalGEF or Ral enhance migration phenotypes of mutations in genes with established roles in cell migration. We used as a model the migration of the canal associated neurons (CANs), and validated our results in HSN cell migration, neurite guidance, and general animal locomotion. These functions of RalGEF and Ral are specific to their control of Ral signaling output rather than other published functions of these proteins. In this capacity Ral functions cell autonomously as a permissive developmental signal. In contrast, we observed Ras, the canonical activator of RalGEF>Ral signaling in cancer, to function as an instructive signal. Furthermore, we unexpectedly identified a function for the close Ras relative, Rap1, consistent with activation of RalGEF>Ral. These studies define functions of RalGEF>Ral, Rap1 and Ras signaling in morphogenetic processes that fashion the nervous system. We have also defined a model for studying how small GTPases partner with downstream effectors. Taken together, this analysis defines novel molecules and relationships in signaling networks that control cell movements during development of the nervous system.

developmental biology↗