Biology subjects

Jensen, E. H.

Publications and source records attributed to Jensen, E. H..

3 recordsLinked to original sources

bioRxiv2026

TFA-defluorinating microbial consortium achieved with analogue enrichment

Trifluoroacetate (TFA) is an ultra-short chain perfluoroalkyl substance (PFAS) and a pollutant of global significance; it is persistent and ubiquitous in the environment across compartments, including food, drinking water, animals, and humans. Concentrations in the environment are rising, concerns over the toxicity of the compound are increasing, and there are currently no efficient ways to remediate TFA pollution, as conventional methods are ineffective at scale under environmental conditions. Microorganisms possessing dehalogenating enzymes targeting the structurally analogous compound monofluoroacetate (MFA) present a potential solution to degrade TFA microbiologically. Due to previously demonstrated dehalogenation of difluoroacetate (DFA) by dehalogenases, the promiscuity of such enzymes was hypothesized to be extendable to TFA as well. In this study cultures obtained from an environmental sample of PFAS contaminated wastewater sludge were incubated in M9 minimal media supplied with 33 mM acetate and either 33 mM TFA, DFA, or MFA in an iterative manner, followed by testing in a 30-day experiment. Free fluoride (F-) was measured at 5 timepoints using a fluoride ion specific electrode (ISE). One culture designated MFA1C significantly degraded MFA, DFA, and TFA (two-way ANOVA mixed model, p < 0.05). MFA1C released 11.2 {+/-} 0.7 M F- which constitutes approximately 0.01% of the potential fluoride release from the total 33 mM TFA applied and with the greatest defluorination activity in the first 9 days of incubation. Fluoride release from TFA and formation of DFA and MFA was confirmed with 19F-NMR. Genetic sequencing and protein-ligand modelling identified two candidate dehalogenase enzymes from Achromobacter denitrificans and Stenotrophomonas sp., respectively, with potential capacity to degrade TFA. The findings of this study are a crucial first step towards future potential bioremediation of TFA, and are, to the best of our knowledge, the first to identify a TFA-degrading consortium of microorganisms.

microbiology↗

bioRxiv2023

Functional glycoproteomics by integrated network assembly and partitioning

The post-translational modification (PTM) of proteins by O-linked {beta}-N-acetyl-D-glucosamine (O-GlcNAcylation) is widespread across the proteome during the lifespan of all multicellular organisms. However, nearly all functional studies have focused on individual protein modifications, overlooking the multitude of simultaneous O-GlcNAcylation events that work together to coordinate cellular activities. Here, we describe Networking of Interactors and SubstratEs (NISE), a novel, systems-level approach to rapidly and comprehensively monitor O-GlcNAcylation across the proteome. Our method integrates affinity purification-mass spectrometry (AP-MS) and site-specific chemoproteomic technologies with network generation and unsupervised partitioning to connect potential upstream regulators with downstream targets of O-GlcNAcylation. The resulting network provides a data-rich framework that reveals both conserved activities of O-GlcNAcylation such as epigenetic regulation as well as tissue-specific functions like synaptic morphology. Beyond O-GlcNAc, this holistic and unbiased systems-level approach provides a broadly applicable framework to study PTMs and discover their diverse roles in specific cell types and biological states.

cell biology↗

bioRxiv2021

Microglia ferroptosis is prevalent in neurodegenerative disease and regulated by SEC24B

Iron dysregulation has been implicated in multiple neurodegenerative diseases, including Parkinsons Disease (PD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS). One prominent feature of affected brain regions are iron-loaded microglia, but how iron overload influences microglia physiology and disease response is poorly understood. Here we show that microglia are highly susceptible to ferroptosis, an iron-dependent form of cell death. In a tri-culture of human iPSC-derived neurons, astrocytes, and microglia, under ferroptosis-inducing conditions, microglia undergo a drastic shift in cell state, with increased ferritin levels, disrupted glutathione homeostasis, and altered cytokine signaling. Similar ferroptosis-associated signature (FAS) microglia were uncovered in PD, and the signature was also found in a large cohort of PD patient blood samples, raising the possibility that ferroptosis can be identified clinically. We performed a genome-wide CRISPR screen which revealed a novel regulator of ferroptosis, the vesicle trafficking gene SEC24B. A small molecule screen also nominated several candidates which blocked ferroptosis, some of which are already in clinical use. These data suggest that ferroptosis sits at the interface of cell death and inflammation, and inhibition of this process in microglia and other brain cells may provide new ways for treating neurodegenerative disease.

neuroscience↗