Biology subjects

Ray, A. E.

Publications and source records attributed to Ray, A. E..

3 recordsLinked to original sources

bioRxiv2026

Trace gas oxidation supports sub-surface microbial communities across Namib Desert fog and aridity gradients

Widely accepted climate predictions indicate that drylands will expand to cover more than half of the Earths terrestrial surface by the end of the 21st century. In these environments, harsh conditions including nutrient and water limitations restrict plant and animal life, thereby increasing the importance of soil microbial communities in nutrient cycling and ecosystem functioning. The Namib Desert is a distinctive dryland ecosystem characterised by a steep natural aridity gradient, transitioning from a coastal hyperarid zone influenced by frequent fog deposition to an inland arid region receiving seasonal rainfall. This study investigates the impact of water availability and moisture regime on microbial trace gas oxidation and community composition across this aridity gradient. Quantitative analyses revealed that total microbial abundance and activity indicators, including ATP concentrations and respiration rates, were significantly (p < 0.005) reduced in hyperarid soils compared to their arid counterparts. In contrast, hyperarid fog-dominated soils exhibited significantly (p < 0.0005) elevated rates of atmospheric hydrogen oxidation, even in the absence of water inputs. We propose that sustained high-affinity hydrogen oxidation, coupled with rapid microbial resuscitation following wetting events, supports shallow sub-surface microbial communities in the Namib Desert, particularly in the coastal hyperarid zone. Together, these findings challenge current understanding of the lower limits of microbial activity and reveal alternate metabolic pathways that enable microbial persistence in hyperarid hot desert soils. ImportanceDrylands are expanding globally, yet the mechanisms that allow microbial life to persist under extreme and sustained water limitation remain poorly understood. This study demonstrates that atmospheric trace gas oxidation, particularly high-affinity hydrogen oxidation, supports active and resilient microbial communities in hyperarid soils of the Namib Desert, even in the absence of liquid water inputs. By revealing how microbes may couple trace gas metabolism to energy and water generation, our findings provide new insight into the lower limits of microbial activity in dry hot desert soils and highlight the need to investigate how microbes persist and sustain soil ecosystem functioning.

microbiology↗

bioRxiv2024

A Quantitative Approach for Assessing Multidrug Resistance in Cancer

Multidrug resistance (MDR) is a primary barrier to successful cancer treatment with small molecule drugs. One mechanism of resistance is through transporters which pump drug out of cancer cells before they exert any therapeutic effect. The most studied transporter is P-glycoprotein (Pgp), a member of the ATP Binding Cassette (ABC) superfamily of drug pumps. Prior research has focused on determining whether drugs are substrates of Pgp. Pgp specificity for FDA approved drugs is currently unclear due to technical variability in assays that quantify enzyme kinetics using non-cellular experimental models. Unfortunately, there is extreme variability in enzyme parameters for drugs that are characterized and gaps in literature for drugs that have not been characterized. Thus, our overall goal is to develop live cell methods to obtain quantitative scores for substrates in cells and fill gaps in the literature. Studying Pgp in the context of MDR, we improve Pgp specificity scores by leveraging new Pgp expression (cell lines, tissues) and function (drug screening) datasets. We experimentally and computationally integrate functional dataset information to better understand Pgp specificity using an approach based on underlying Michaelis-Menten enzyme kinetics. We obtain consensus scores for Pgp specificity across [~]150 FDA approved oncology drugs and validate them experimentally in a subset of 76 substrates selected to represent the spectrum of drugs for Pgp specificity. These scores can be used to calibrate clinical diagnostics (Pgp expression), and our experimental platform can be used to quantify Pgp function in clinical samples. Overall, we develop a parallel computational and experimental procedure to estimate Pgp selectivity in live cells. This procedure can be expanded to other drug transporters which contribute to MDR to further characterize this phenotype quantitatively. Significance StatementMDR is facilitated through the action of drug transporters which are upregulated in cancer. Even though selective inhibitors have been designed to decrease drug efflux, they failed clinically. So, current clinical practice is to select non-substrates. However, non-substrates are difficult to define. Here, we have developed a quantitative platform for characterizing MDR in cancer that factors in gene expression and enzyme kinetics. Our computational and experimental platform successfully identified the spectrum of substrates for Pgp from the FDA approved oncology drug library. This quantitative approach reflects the multigene phenotype of cancer drug resistance and can be applied to other MDR transporter genes to optimize drug selection clinically.

biochemistry↗

bioRxiv2024

The balance between antiviral and antibacterial responses during M. Tuberculosis infection is regulated by the ubiquitin ligase CBL

As a first line of host defense, macrophages must be able to effectively sense and respond to diverse types of pathogens, and while a particular type of immune response may be beneficial in some circumstances, it can be detrimental in others. Upon infecting a macrophage, M. tuberculosis (Mtb) induces proinflammatory cytokines that activate antibacterial responses. Surprisingly, Mtb also triggers antiviral responses that actually hinder the ability of macrophages to control Mtb infection. The ubiquitin ligase CBL suppresses these antiviral responses and shifts macrophages toward a more antibacterial state during Mtb infection, however, the mechanisms by which CBL regulates immune signaling are unknown. We found that CBL controls responses to multiple stimuli and broadly suppresses the expression of antiviral effector genes. We then used mass-spectrometry to investigate potential CBL substrates and identified over 46,000 ubiquitylated peptides in Mtb-infected macrophages, as well as roughly 400 peptides with CBL-dependent ubiquitylation. We then performed genetic interaction analysis of CBL and its putative substrates, and identified the Fas associated factor 2 (FAF2) adapter protein as a key signaling molecule protein downstream of CBL. Together, these analyses identify thousands of new ubiquitin-mediated signaling events during the innate immune response and reveal an important new regulatory hub in this response.

immunology↗