Biology subjects

Hodge, E. A.

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

5 recordsLinked to original sources

bioRxiv2025

Conservation of sensory pathways implies a localised change in the mushroom bodies is associated with cognitive evolution in Heliconius butterflies

Acquisition of novel behaviour is reflected in changes in sensory investment or integration, but the exact nature of these changes is often unclear. Within the Neotropical butterfly tribe, Heliconiini, the genus Heliconius possess 4-fold larger mushroom bodies, an insect learning and memory centre, than closely related Heliconiini. Mushroom body expansion in Heliconius co-occurred with a dietary innovation, and is associated with systematic spatial foraging and extended lifespans. Heliconiini therefore offer an attractive system for studying how behavioural evolution is facilitated by changes in neural systems. Heliconius foraging relies on visual scene memories and, indeed, Heliconius have more stable visual long-term memory, and evidence of visual specialisation in the mushroom bodies. Here, we explore how vision-specific neuroanatomical and behavioural enhancement in Heliconius impacts sensory pathways upstream of the mushroom bodies by assessing investment across the eyes, sensory structures and projection pathways. Despite evidence of refinement in visually-based behaviour, we found no increased investment in visual structures, brain areas or pathways. This suggests that the rapid expansion of the Heliconius mushroom body occurred in a context of conserved detection and processing of visual cues, and that a localised shift within integrative brain centres facilitated the evolution of Heliconius novel behaviours.

evolutionary biology↗

bioRxiv2025

Distinct evolutionary trajectories of two integration centres, the central complex and mushroom bodies, across Heliconiini butterflies

Neural circuits have evolved to produce cognitive processes that facilitate a species variable behavioural repertoire. Underlying this variation are evolutionary forces, such as selection, that operate on changes to circuitry against a background of constraints. The interplay between selection and potentially limiting constraints determine how circuits evolve. Understanding how this process operates requires an evolutionary framework that facilitates comparative analysis of neural traits, within a clear behavioural and functional context. We leverage a large radiation of Heliconiini butterflies to examine how selection shapes the evolution of the central complex and the mushroom bodies, two integration centres in the insect brain involved in spatial navigation. Within the Heliconiini, one genus, Heliconius, performs systematic spatial foraging and navigation to exploit specific plants as a source of pollen, a novel dietary resource. Closely related genera within Heliconiini lack this dietary adaptation, and are more vagrant foragers. The evolution of increased spatial fidelity in Heliconius has led to changes in brain morphology, and in specific learning and memory profiles, over a relatively short evolutionary time scale. Here, using a dataset of 41 species, we show that in contrast to a massive expansion of the mushroom bodies, the central complex and associated visual processing areas are strongly conserved in size and general architecture. We corroborate this by characterising patterns of fine anatomical conservation, including conserved patterns in dopamine and serotonin expression. However, we also identify a divergence in the expression of a neuropeptide, Allatostatin A, in the noduli, and in the numbers of GABA-ergic ellipsoid body ring neurons and their branching in the fan-shaped body, which are essential members of the anterior compass pathway. These differences match expectations of where evolutionary adaptability might occur inside the central complex network and provide rare examples of divergence of these circuits in a shallow phylogenetic context. We conclude that due to the contrasting volumetric conservation of the central complex and the massive volumetric differences in the mushroom bodies, their circuit logics must determine distinct responses to selection associated with divergent foraging behaviours.

neuroscience↗

bioRxiv2021

Cryo-ET of HIV reveals Env positioning on Gag lattice and structural variation among Env trimers

HIV-1 Env mediates viral entry into host cells and is the sole target for neutralizing antibodies. However, Env structure and organization in its native virion context has eluded detailed characterization. Here we used cryo-electron tomography to analyze Env in mature and immature HIV-1 particles. Immature particles showed distinct Env positioning relative to the underlying Gag lattice, providing insights into long-standing questions about Env incorporation. A 9.1[A] sub-tomogram averaged reconstruction of virion-bound Env in conjunction with structural mass spectrometry revealed unexpected features, including a variable central core of the gp41 subunit, heterogeneous glycosylation between protomers plus a flexible stalk that allows Env tilting and variable exposure of neutralizing epitopes. Together, our results provide an integrative understanding of HIV assembly and structural variation in Env antigen presentation.

biophysics↗

bioRxiv2021

Changes at V2 apex of HIV-1 Clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies

HIV-1 clade C envelope immunogens that elicit both neutralizing and non-neutralizing V1V2-scaffold specific antibodies (protective correlates from RV144 human trial) are urgently needed due to the prevalence of this clade in the most impacted regions worldwide. To achieve this, we introduced structure-guided changes followed by consensus-C sequence-guided optimizations at the V2-region to generate UFO-v2-RQH173 trimer. This improved the abundance of native-like trimers and carried an intrinsic dynamic V2-loop. Following immunization of rabbits, the wild-type protein failed to elicit any autologous neutralizing antibodies but UFO-v2-RQH173 elicited both autologous neutralizing and broad V1V2-scaffold antibodies. The variant with 173Y modification in V2-region, most prevalent among HIV-1 sequences, showed decreased ability in displaying native-like V1V2 epitope with time in-vitro and elicited antibodies with lower neutralizing and higher V1V2-scaffold activities. Our results identify a clade C C.1086-UFO-v2-RQH173 trimer capable of eliciting improved neutralizing and V1V2-scaffold antibodies, and reveal the importance of V2-region in tuning this.

immunology↗

bioRxiv2020

Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2

A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, we describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

immunology↗