Biology subjects

Alston, J.

Publications and source records attributed to Alston, J..

3 recordsLinked to original sources

bioRxiv2023

Conserved molecular recognition by an intrinsically disordered region in the absence of sequence conservation

Intrinsically disordered regions (IDRs) are critical for cellular function, yet often appear to lack sequence conservation when assessed by multiple sequence alignments. This raises the question of if and how function can be encoded and preserved in these regions despite massive sequence variation. To address this question, we have applied coarse-grained molecular dynamics simulations to investigate non-specific RNA binding of coronavirus nucleocapsid proteins. Coronavirus nucleocapsid proteins consist of multiple interspersed disordered and folded domains that bind RNA. We focussed here on the first two domains of coronavirus nucleocapsid proteins, the disordered N-terminal domain (NTD) followed by the folded RNA binding domain (RBD). While the NTD is highly variable across evolution, the RBD is structurally conserved. This combination makes the NTD-RBD a convenient model system to explore the interplay between an IDR adjacent to a folded domain, and how changes in IDR sequence can influence molecular recognition of a partner. Our results reveal a surprising degree of sequence-specificity encoded by both the composition and the precise order of the amino acids in the NTD. The presence of an NTD can - depending on the sequence - either suppress or enhance RNA binding. Despite this sensitivity, large-scale variation in NTD sequences is possible while certain sequence features are retained. Consequently, a conformationally-conserved fuzzy RNA:protein complex is found across nucleocapsid protein orthologs, despite large-scale changes in both NTD sequence and RBD surface chemistry. Taken together, these insights shed light on the ability of disordered regions to preserve functional characteristics despite their sequence variability.

biophysics↗

bioRxiv2020

Nutrient sensing pathways regulating adult reproductive diapause in C. elegans

Genetic and environmental manipulations, such as dietary restriction (DR), can improve both health span and lifespan in a wide range of organisms, including humans. Changes in nutrient intake trigger often overlapping metabolic pathways that can generate distinct or even opposite outputs depending on several factors, such as when DR occurs in the lifecycle of the organism or the nature of the changes in nutrients. Due to the complexity of metabolic pathways and the diversity in outputs, the underlying mechanisms regulating diet-associated pro-longevity are not yet well understood. Adult reproductive diapause (ARD) in the model organism Caenorhabditis elegans is a DR model that is associated with lengthened lifespan and reproductive potential (Angelo and Van Gilst 2009). As the metabolic pathways regulating ARD have not yet been explored in depth, we performed a candidate-based genetic screen analyzing select nutrient-sensing pathways to determine their contribution to the regulation of ARD. Focusing on the three phases of ARD (initiation, maintenance, and recovery), we find that ARD initiation is regulated by fatty acid metabolism, sirtuins, AMPK, and the O-linked N-acetyl glucosamine (O-GlcNAc) pathway. Although ARD maintenance was not significantly influenced by the nutrient sensors in our screen, we found that ARD recovery was modulated by energy sensing, stress response, insulin-like signaling, and the TOR pathway. We also discovered that fatty acid {beta}-oxidation regulates ARD initiation through a pathway involving the O-GlcNAc cycling enzyme, OGT-1, acting with the nuclear hormone receptor NHR-49. Consistent with these findings, our analysis revealed a change in levels of neutral lipids associated with ARD entry defects. Our findings thus identify novel conserved genetic pathways required for ARD entry and recovery and identify new genetic interactions that provide insight into the role of OGT and OGA.

genetics↗

bioRxiv2018

Roost selection by male northern long-eared bats (Myotis septentrionalis) at their western range edge

Conservation in multi-use landscapes requires identifying and conserving critical resources for imperiled species because those resources may otherwise be destroyed or degraded by human activity. Summer day-roost sites are critical resources for bats, so conserving roost sites is thus an important component of many bat conservation plans. We used VHF telemetry to identify and characterize summer day-roost selection by male northern long-eared bats (Myotis septentrionalis) at the western edge of their range in South Dakota, USA. We tracked 18 bats to 43 tree roosts and used an information theoretic approach to determine the relative importance of tree- and plot-level characteristics on roost site selection. Bats selected roost trees that were larger in diameter, more decayed, closer to more snags, and under denser canopy than other trees available on the landscape. Protecting large-diameter snags within intact forest is important for the conservation of this federally threatened species, particularly along the western edge of its range where it may be subject to range contraction and local extinction. Protecting short ([≤] 3 m) snags in particular may be a low-risk, high-reward strategy for conservation of resources important to male northern long-eared bats.

zoology↗