Biology subjects

Salazar, M. A.

Publications and source records attributed to Salazar, M. A..

3 recordsLinked to original sources

bioRxiv2024

Eco-Microbiology: Discovering Biochemical Enhancers of PET Biodegradation by Piscinibacter sakaiensis

The scale of plastic pollution boggles the mind. Nearly 400 megatons of virgin plastics are produced annually, with an environmental release rate of 80 percent; and plastic waste including micro- and nanoplastics are associated with a plethora of problems. The naturally evolved abilities of plastic-degrading and consuming microbes offer a starting point for generating sustainable and eco-centric solutions to plastic pollution. Here we developed an iterative discovery procedure coupling faster quasi-high-throughput polyethylene terephthalate (PET) dependent bioactivity screens with longer-term PET biodegradation assays to find small molecule and ionic boosters of PET consumption by the bacterium Piscinibacter sakaiensis. We discovered multiple hits supporting greater than 2-fold enhancement of PET biodegradation - with hits belonging to a small but heterogeneous set of compounds and mixtures, suggesting upregulation of PET consumption via multiple paths. This work has the potential to advance the creation of a fermentation-based process for solving PET plastic pollution. ImportancePlastic pollution is an urgent environmental issue. In addition, micro- and nanoplastics (MNPs) have become an acute source of worry with discoveries of the global distribution and transport of MNPs, their presence within a diversity of organisms including common foodstuffs and human tissues, and their potential association with declining fertility and various disease states. Solutions are needed and the microbial world offers abundant help via naturally evolved biodegraders of plastic waste. We created a non-genetic method to accelerate polyethylene terephthalate (PET) plastic biodegradation by Piscinibacter sakaiensis, a bacterium that evolved to slowly but completely consume PET. Our method entails a combination of plastic-dependent bioactivity screens and slower biodegradation tests to find extrinsic biochemical stimulators of PET biodegradation. The conditions we found boost PET biodegradation by over two-fold and provide a foundation for further studies to realize a fermentation-based process needed to solve PET plastic pollution.

microbiology↗

bioRxiv2023

Selective advantage of mutant stem cells in clonal hematopoiesis occurs by attenuating the deleterious effects of inflammation and aging

Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSC) acquire mutations in genes, including DNMT3A and TET2, conferring a competitive advantage through a mechanism that remains unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on CH bone marrow samples. Most of the selective advantage of mutant cells occurs within HSCs. DNMT3A and TET2-mutant clones expand further in early progenitors, while TET2 mutations accelerate myeloid maturation in a dose-dependent manner. Unexpectedly, both mutant and non-mutant HSCs from CH samples are enriched for inflammatory and aging transcriptomic signatures, compared to HSC from non-CH samples, revealing a non-cell autonomous mechanism. However, DNMT3A and TET2-mutant HSCs have an attenuated inflammatory response relative to wild-type HSCs within the same sample. Our data support a model whereby CH clones are gradually selected because they are more resistant to the deleterious impact of inflammation and aging.

cancer biology↗

bioRxiv2021

A simple and direct method to define clonal selection in somatic mosaicism

As DNA variants accumulate in somatic stem cells, become selected or evolve neutrally, they may ultimately alter tissue function. When, and how, selection occurs in homeostatic tissues is incompletely understood. Here, we introduce SCIFER, a scalable method that identifies selection in an individual tissue, without requiring knowledge of the underlying driver event. Moreover, SCIFER infers the self-renewal and mutation dynamics of the tissues stem cells, and, if selection is present, the size and growth rate of the largest selected clone. We benchmark SCIFER with published data and then probe bone marrow of 22 non-leukemic individuals for clonal hematopoiesis (CH), identifying CH with known and unknown driver events. Unexpectedly, we find accelerated division of all stem cells in CH, compared to age-matched non-CH individuals, suggesting that the bone marrow environment alters stem cell dynamics in individuals with CH. SCIFER is broadly applicable to renewing somatic tissues to detect and quantify selection.

cancer biology↗