Biology subjects

Goldstone, E. B.

Publications and source records attributed to Goldstone, E. B..

4 recordsLinked to original sources

bioRxiv2026

RNA Sequencing in Adult Drosophila Females Identifies Estrogen-Related Receptor-Dependent Transcriptional Changes in Metabolism, DNA Replication, and Translation

Nuclear receptors, transcription factors essential for organism growth, development, and reproduction, are expressed in a variety of tissues, with some exhibiting differential expression between males and females. The Estrogen-related receptor (ERR) is a conserved metabolic nuclear receptor required for energy metabolism and lipid accumulation. While previous studies in Drosophila have identified potential ERR targets from mixed sex larval populations and adult males, it is unclear whether transcriptional targets and biological pathways downstream of ERR are altered in a sex-specific manner. Here, we took an RNA sequencing approach to identify candidate ERR targets specifically in adult females and compared differentially expressed genes to a published male-specific dataset. Whole body conditional knockout of ERR significantly downregulated transcription of enzymes associated with glycolysis and the pentose phosphate pathway. In contrast, components of the DNA replication machinery were selectively downregulated in adult females, whereas ribosome biogenesis transcription was increased. Our results have further defined the metabolic targets of ERR between males and females, as well as suggest that ERR regulates DNA replication and global translation in females. SUMMARYIn this manuscript, we used RNA sequencing to identify differential expression of transcripts dependent on the nuclear receptor ERR in Drosophila adult females. We find that ERR is required for activating transcription of glycolytic and pentose phosphate pathway enzymes, as observed in larvae and adult males. Furthermore, compared to males, loss of ERR in females specifically decreased DNA replication enzyme components while upregulating ribosomal components. Our results suggest that nuclear receptors have common and sex-specific targets, which will be of interest for those in the nuclear receptor and sexual dimorphism fields.

physiology↗

bioRxiv2025

Chemokinesis by a microbial predator

Regulated motility is vital for many cells--both for unicellular microbes and for cells within multicellular bodies. Different conditions require different rates and directions of movement. For the microbial predator Capsaspora owczarzaki, its motility is likely essential for predation. This organism has been shown to prey on diverse organisms, including the schistosome parasites that co-reside with it in Biomphalaria glabrata snails. Capsaspora is also an evolutionary model for the unicellular ancestor of animals. This phylogenic placement makes Capsasporas motility an attractive target for understanding the evolution of motility in animal cells. Until now, little was known of how Capsaspora regulates it rate and direction of motility. Here we found that it exhibits chemokinesis (increased movement in response to chemical factors) in response to proteins released from prey cells. Chemokinesis also occurs in response to pure proteins--including bovine serum albumin. We found that this chemokinesis behavior is dependent on Capsaspora cell density, which suggests that the regulated motility is a cooperative behavior (possibly to improve cooperative feeding). We developed a mathematical model of Capsaspora motility and found that chemokinesis alone does not benefit Capsaspora predation. However, when coupled with chemotaxis (directional motility along a chemical gradient toward prey), chemokinesis may improve predation. Finally, we quantitatively analyzed Capsasporas previously reported chemotaxis behavior. These findings lay a foundation for characterizing the mechanisms of regulated motility in a predator of a human pathogen and a model for the ancestor of animals.

biochemistry↗

bioRxiv2024

Exogenous lipid vesicles induce endocytosis-mediated cellular aggregation in a close unicellular relative of animals

Capsaspora owczarzaki is a protozoan that may both reveal aspects of animal evolution and also curtail the spread of schistosomiasis, a neglected tropical disease. Capsaspora exhibits a chemically regulated aggregative behavior that resembles cellular aggregation in some animals. This behavior may have played a key role in the evolution of animal multicellularity. Additionally, this aggregative behavior may be important for Capsasporas ability to colonize the intermediate host of parasitic schistosomes and potentially prevent the spread of schistosomiasis. Both applications demand elucidation of the molecular mechanism of Capsaspora aggregation. Toward this goal, we first determined the necessary chemical properties of lipid cues that activate aggregation. We found that a wide range of abundant zwitterionic lipids induced aggregation, revealing that the aggregative behavior could be activated by diverse lipid-rich conditions. Furthermore, we demonstrated that aggregation in Capsaspora requires clathrin-mediated endocytosis, highlighting the potential significance of endocytosis-linked cellular signaling in recent animal ancestors. Finally, we found that aggregation was initiated by post-translational activation of cell-cell adhesion--not transcriptional regulation of cellular adhesion machinery. Our findings illuminate the chemical, molecular and cellular mechanisms that regulate Capsaspora aggregative behavior--with implications for the evolution of animal multicellularity and the transmission of parasites.

biochemistry↗

bioRxiv2024

Host lipids regulate multicellular behavior of a predator of a human pathogen

As symbionts of animals, microbial eukaryotes benefit and harm their hosts in myriad ways. A model microeukaryote (Capsaspora owczarzaki) is a symbiont of Biomphalaria glabrata snails and may prevent transmission of parasitic schistosomes from snails to humans. However, it is unclear which host factors determine Capsasporas ability to colonize snails. Here, we discovered that Capsaspora forms multicellular aggregates when exposed to snail hemolymph. We identified a molecular cue for aggregation: a hemolymph-derived phosphatidylcholine, which becomes elevated in schistosome-infected snails. Therefore, Capsaspora aggregation may be a response to the physiological state of its host, and it may determine its ability to colonize snails and exclude parasitic schistosomes. Furthermore, Capsaspora is an evolutionary model organism whose aggregation may be ancestral to animals. This discovery, that a prevalent lipid induces Capsaspora multicellularity, suggests that this aggregation phenotype may be ancient. Additionally, the specific lipid will be a useful tool for further aggregation studies.

biochemistry↗