I am honored and humbled to receive the E. B. Wilson Medal and happy to share some reflections on my journey as a cell biologist. It took me a while to realize that my interest in biology would center on how cells are spatially and dynamically organized. From an initial fascination with cellular structures I came to appreciate that cells exhibit dynamism across all scales-from their molecules, to molecular complexes, to organelles. Uncovering the principles of this dynamism, including new ways to observe and quantify it, has been the guiding star of my work.

Animal models have been widely used to gain insight into the mechanisms underlying the acute and long-term effects of alcohol exposure. The fruit fly Drosophila melanogaster encounters ethanol in its natural habitat and possesses many adaptations that allow it to survive and thrive in ethanol-rich environments. Several assays to study ethanol-related behaviors in flies, ranging from acute intoxication to self-administration and reward, have been developed in the past 20 years. These assays have provided the basis for studying the physiological and behavioral effects of ethanol and for identifying genes mediating these effects. In this review we describe the ecological relationship between flies and ethanol, the effects of ethanol on fly development and behavior, the use of flies as a model for alcohol addiction, and the interaction between ethanol and social behavior. We discuss these advances in the context of their utility to help decipher the mechanisms underlying the diverse effects of ethanol, including those that mediate ethanol dependence and addiction in humans.

A number of aphid species produce individuals, termed soldiers, that defend the colony by attacking predators. Soldiers have either reduced or zero direct reproductive fitness. Their behavior is therefore altruistic in the classical sense: an individual is behaving in a way that incurs reproductive costs on itself and confers reproductive benefits on another. However, comparison with the better–known eusocial insects (Hymenoptera, Isoptera) indicates that there are important differences between clonal and sexual social animals.

Here we take a clone's–eye view and conclude that many facets of aphid sociality are best thought of in terms of resource allocation: for example, the choice between investment in defense and reproduction. This view considerably simplifies some aspects of the problem and highlights the qualitatively different nature of genetic heterogeneity in colonies of aphids and of other social insects. In sexually reproducing social insects, each individual usually has a different genome, which leads to genetic conflicts of interest between individuals. In social aphids, all members of a clone have identical genomes, barring new mutations, and there should be no disagreement among clonemates about investment decisions. Genetic heterogeneity within colonies can arise, but principally through clonal mixing, and this means that investment decisions will vary between different clones rather than among all individuals.

1. Defensive individuals, termed soldiers, have recently been discovered in aphids, Soldiers are typically early instar larvae, and in many species the soldiers are reproductively sterile and morphologically and behaviourally specialized. 2. Since aphids reproduce parthenogenetically, we might expect soldier production to be more widespread in aphids than it is. We suggest that a more useful way to think about these problems is to attempt to understand how a clone (rather than an individual) should invest in defence and reproduction. 3. Known soldiers are currently restricted to two families of aphids, the Pemphigidae and Hormaphididae, although they are distributed widely among genera within these families. We discuss the use of a phylogenetic perspective to aid comparative studies of soldier production and we demonstrate this approach using current estimates of phylogenetic affinities among aphids. We show that the distribution of soldier production requires a minimum of six to nine evolutionary origins plus at least one loss. 4. At least four main types of soldiers exist and we present and discuss this diversity of soldiers. 5. Most soldier-producing species produce soldiers within plant galls and we discuss the importance of galls for the evolution of soldiers. 6. We summarize the evidence on the interactions between soldiers and predators and between soldier-producing aphids and ants. 7. We present an optimality model for soldier investment strategies to help guide investigations of the ecological factors selecting for soldiers. 8. The proximate mechanisms of soldier production are currently very poorly understood and we suggest several avenues for further research.

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer.

The extracellular matrix (ECM) regulates cell migration and sculpts organ shape. AdamTS proteins are extracellular metalloproteases known to modify ECM proteins and promote cell migration, but demonstrated roles for AdamTS proteins in regulating CNS structure and ensuring cell lineages remain fixed in place have not been uncovered. Using forward genetic approaches in Drosophila, we find that reduction of AdamTS-A function induces both the mass exodus of neural lineages out of the CNS and drastic perturbations to CNS structure. Expressed and active in surface glia, AdamTS-A acts in parallel to perlecan and in opposition to viking/collagen IV and βPS-integrin to keep CNS lineages rooted in place and to preserve the structural integrity of the CNS. viking/collagen IV and βPS-integrin are known to promote tissue stiffness and oppose the function of perlecan, which reduces tissue stiffness. Our work supports a model in which AdamTS-A anchors cells in place and preserves CNS architecture by reducing tissue stiffness.

Recent years have seen a rise in publications demonstrating coupling between transcription and mRNA decay. This coupling most often accompanies cellular processes that involve transitions in gene expression patterns, for example during mitotic division and cellular differentiation and in response to cellular stress. Transcription can affect the mRNA fate by multiple mechanisms. The most novel finding is the process of co-transcriptional imprinting of mRNAs with proteins, which in turn regulate cytoplasmic mRNA stability. Transcription therefore is not only a catalyst of mRNA synthesis but also provides a platform that enables imprinting, which coordinates between transcription and mRNA decay. Here we present an overview of the literature, which provides the evidence of coupling between transcription and decay, review the mechanisms and regulators by which the two processes are coupled, discuss why such coupling is beneficial and present a new model for regulation of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms.

The structure of compound eyes in arthropods has been the subject of many studies, revealing important biological principles. Until recently, these studies were constrained by the two-dimensional nature of available ultrastructural data. By taking advantage of the novel three-dimensional ultrastructural dataset obtained using volume electron microscopy, we present the first cellular-level reconstruction of the whole compound eye of an insect, the miniaturized parasitoid wasp Megaphragma viggianii. The compound eye of the female M. viggianii consists of 29 ommatidia and contains 478 cells. Despite the almost anucleate brain, all cells of the compound eye contain nuclei. As in larger insects, the dorsal rim area of the eye in M. viggianii contains ommatidia that are believed to be specialized in polarized light detection as reflected in their corneal and retinal morphology. We report the presence of three 'ectopic' photoreceptors. Our results offer new insights into the miniaturization of compound eyes and scaling of sensory organs in general.

Preprint:  https://doi.org 10.1101/2024.09.30.615804

The brain's synaptic networks endow an animal with powerfully adaptive biological behavior. Maps of such synaptic circuits densely reconstructed in those model brains, which can be examined and manipulated by genetic means, offer the best prospect for understanding the underlying biological bases of behavior. That prospect is now technologically feasible and a scientifically enabling possibility in neurobiology, much as genomics has been in molecular biology and genetics. In , two major advances are in electron microscopic technology, using focused ion beam-scanning electron microscopy (FIB-SEM) milling to capture and align digital images, and in computer-aided reconstruction of neuron morphologies. The last decade has witnessed enormous progress in detailed knowledge of the actual synaptic circuits formed by real neurons. Advances in various brain regions that heralded identification of the motion-sensing circuits in the optic lobe are now extending to other brain regions, with the prospect of encompassing the fly's entire nervous system, both brain and ventral nerve cord. Expected final online publication date for the Volume 35 is October 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.