Title: Variation in the status of Acropora palmata coral in relation to environmental factors along the west coast of Barbados

Authors: Hana Kaloudis [1], Eleanore Lukas [1], Faye Dryden [1], Lindsey Myhre [1], Atisha Lloyd [1], Virginie Millien [1] 

Affiliations: [1] Faculty of Science, McGill University, Montreal, QC, Canada [2] Faculty of Science and Technology, University of the West Indies at Cave Hill, Saint Michael, Barbados 

Keywords: Acropora palmata; Barbados; Breakwater; Coral health index; Latitude; Runoff output

Abstract: Acropora palmata is a critically endangered Caribbean coral whose decline threatens both coastal ecosystems and shoreline protection. Barbados once supported extensive A. palmata colonies along its west coast, yet the environmental drivers shaping current patterns of colony health and distribution remain unclear. We re-surveyed twelve sites in 2025,five of which were also assessed in 2024 and all originally mapped in 2015,to evaluate temporal changes in colony abundance, size, and condition, and to test how spatial and environmental gradients influence A. palmata health. Average colony height increased from 2015 to 2024, but declined sharply in 2025, which is consistent with fragmentation following heavy wave action and Hurricane Beryl in 2024. Despite this size reduction, health index scores improved significantly from 2024 to 2025, indicating rapid recovery in live tissue and pigmentation since the 2024 bleaching and hurricane events. Lack of pattern in count over the study years show that different conditions across sites had varying impacts on abundance. Our PCA results revealed four distinct habitat groupings across the coastline, with strong environmental gradients associated with latitude, distance to breakwaters and runoff outputs, depth, and distance from shore. Percent dead tissue was significantly related to a depth/distance to shoreline gradient, colony abundance was strongly structured by latitude, and total colony area increased significantly along the same gradient. Distances to individual anthropogenic structures were not associated with colony condition once broader spatial gradients were considered. Collectively, these results indicate that A. palmata conditions along Barbados’s west coast are shaped primarily by latitudinal environmental variation rather than direct proximity to runoff outputs or breakwaters. These findings provide an updated baseline for restoration planning and highlight the importance of spatial context in the management of recovering A. palmata populations.

 

 

 

Title: Engineering SPEF1 Fusion Proteins for Improved Microtubule Seam Alignment for Cryo-Electron Microscopy

Authors: Helena Goodey-Parfitt [1], Tina Alagha [1], Hayley Rose Blythe [1], Thibault Legal [1], Khanh Huy Bui [1]

Affiliations: [1] Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada

Keywords: Computational protein design; Cryo-electron microscopy; Fusion proteins; Microtubule seam; Microtubules; Sperm flagellar protein 1 (SPEF1)

Abstract: Microtubules are dynamic polymers of α-β tubulin heterodimers that support cell structure and contribute to processes including cell division, intracellular transport, and cilia stability. Their functions are modulated by microtubule-associated proteins (MAPs), which regulate microtubule assembly, stability, organization, and interactions with other cellular components. Accurate identification of the microtubule seam, where heterotypic α-β interactions replace homotypic α-α and β-β contacts, is essential for cryo-electron microscopy (cryo-EM) reconstruction. Current seam-alignment strategies employ kinesin motor domains that generate alignment contrast but mask lattice features and limit compatibility with many MAPs. The Bui lab identified Sperm Flagellar Protein 1 (SPEF1) as a seam-binding alternative, though its small size limits reliable visualization. We hypothesised that engineering larger SPEF1 fusion proteins would improve seam contrast and alignment while preserving microtubule binding. Fusion constructs were designed using RoseTTAFold Diffusion to append structured domains to the SPEF1 microtubule-binding region while preserving predicted folding and function. Constructs were cloned, sequence-verified, and expressed in Escherichia coli, with several designs demonstrating strong expression and yielding soluble protein after purification. Using a microtubule co-sedimentation assay, the engineered construct SPEF1 (1-120)-300AA demonstrated effective binding to polymerized microtubules, supporting its suitability for further microtubule seam-targeting studies, although cryo-EM validation remains ongoing. These results position engineered SPEF1 fusion proteins as promising seam-alignment tools that provide a broadly compatible and experimentally validated strategy for advancing cryo-EM studies of microtubule architecture and enabling direct evaluation of seam localization without masking lattice features or disrupting lattice-binding protein interactions, thereby overcoming limitations imposed by existing seam-alignment strategies.

 

 

 

 

Title: Impact of human-like knock-in mutation on glomerular structure in a mouse model of Sanfilippo Syndrome (MPS IIIC)

Authors: Emily Pun [1], Dr. Lorena Carvelli [1], Dr. Alexey V. Pshezhetsky [1], Dr. Carlos R. Morales [1]

Affiliations: [1] Department of Anatomy and Cell Biology, McGill University

Keywords: Heparan sulfate, Lysosomal storage disorder, Renal pathology, Sanfilippo syndrome C

Mucopolysaccharidosis type IIIC, also known as Sanfilippo syndrome type C, is a lysosomal storage disease caused by a deficiency of heparan sulfate acetyl-CoA: alpha glucosaminide N-acetyltransferase (HGSNAT). HGSNAT is one of the key enzymes involved in the degradation of heparan sulfate, a glycosaminoglycan present in proteoglycans and basement membranes. The absence of HGSNAT activity leads to an accumulation of heparan sulfate in lysosomes, causing cellular dysfunction and progressive neurological degeneration. This study examined the glomerular renal pathology in a CRISPR-Cas9-generated knock-in mouse model expressing the Pro304Leu HGSNAT variant, which replicates the human Pro311Leu mutation. The model showed early-onset MPS IIIC with dominant-negative effects and stress on the endoplasmic reticulum and lysosomes. Wild type (WT, n=3, 7 months old) and HGSNAT knock-in (KI, n=3, 7 months old) mice were used for each experiment. Kidneys were collected and processed for histological and ultrastructural analysis by light and electron microscopy. ImageJ was used to quantify the stained area of the mesangial matrix. Compared with WT, KI mice exhibited a more intense Periodic acid Schiff staining of the glomerular mesangial matrix, an accumulation of empty vesicles in the podocytes, distorted mesangial cells, and severely affected podocytes filled with lysosomes and enlarged pedicels. In conclusion, the increased deposition of heparan sulfate in the mesangial matrix is associated with glomerular distortion and mesangial proliferation, findings that could be consistent with the development of mesangial proliferative glomerulonephritis.

 

 

Title: Understanding the impact of antigen-specific regulatory T cells on anergy induction in vivo

Authors: Sophie Courville1, Stefanie F. Valbon2,3, Marilaine Fournier3, Heather J. Melichar3,4

Affilitations: 1Department of Physiology, McGill University, Montreal Qc, Canada2Department of Microbiology, Immunology and Infectious Disease, Université de Montréal, Montreal, Qc, Canada

3Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, Qc, Canada

4 Department of Microbiology and Immunology, McGill University, Montreal Qc, Canada

Keywords: Adoptive cell transfer; Antigen-specific regulatory T cells; Peripheral tolerance; Single-cell RNA sequencing; T Cell Anergy

Abstract: 

In order to properly function, the immune system must achieve a fine balance between attacking foreign invaders while avoiding damage to healthy (self) tissue. One way it maintains this balance is through the induction of T cell anergy. Anergy is a key tolerance mechanism that renders self-reactive T cells hyporesponsive, thereby preventing the development of autoimmune diseases. T cell anergy is typically induced under steady state conditions when antigen recognition occurs without co-stimulation, such as in the absence of inflammation. Regulatory T (Treg) cell-mediated suppression of self-reactive T cells may contribute to anergy induction, but their specific role remains poorly defined. In this study, we investigate how antigen-specific Tregs influence the generation and accumulation of anergic CD8 T cells in vivo. To test this, we generated Tregs ex vivo from OVA-specific OT-II CD4 T cells. We injected OVA-specific OT-I CD8 T cells with or without OT-II Tregs into mice expressing OVA as a model self-antigen. After fourteen days, we observed an increase in the proportion of OT-I T cells in the spleen of mice co-adoptively transferred with OT-II Tregs as compared to mice injected with OT-I T cells alone. We confirmed, via ex vivo re-stimulation, that OT-I T cells induced in the presence of OT-II Tregs remained anergic. Interestingly, single-cell RNA-sequencing revealed that levels of antigen-specific Tregs correlate with transcriptional heterogeneity among anergic CD8 T cells in vivo. These findings suggest that antigen-specific Tregs promote the accumulation of anergic CD8 T cells. This work contributes to a broader effort to define mechanisms of peripheral tolerance, providing a foundation for their potential use in therapeutic interventions to prevent autoimmune disease.

 

Title: Computational Model of the Hippocampus Supports Exploratory Behaviour in Reinforcement Learning Agents

Authors: Sabrina Du1, Adel Halawa1,2, Aleksei Efremov1,2, Adrien Peyrache1, Daniel Levenstein3, Blake Richards1,2,3,4,5

Affiliations: 1Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

2Mila, Montreal, QC, Canada

3Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut, United States of America

4School of Computer Science, McGill University, Montreal, QC, Canada

5Learning in Machines and Brains Program, CIFAR, Toronto ON, Canada

Keywords: Hippocampus; Cognitive maps; Intrinsic Reinforcement Learning; Curiosity-Driven Exploration

Abstract: 

The hippocampus supports spatial navigation, memory, and planning through the formation of a cognitive map: a structured environmental representation reflected in its neural activity. These neural dynamics can be modeled computationally using recurrent neural networks (RNNs) to provide insights into how cognitive maps guide behavior. However, these RNNs are typically trained via reinforcement learning (RL) using external rewards, failing to capture the intrinsic drive of freely exploring animals in the absence of external rewards. Instead, reward-free RL models, which rely on internal environmental representations, are better candidates to study novelty-seeking and exploratory behaviour. This study aims to investigate whether an RNN exhibiting hippocampal-like activity builds spatial representations sufficient to support exploratory behavior in reward-free RL agents. We leveraged an existing RNN trained for sensory sequence prediction, which exhibits hippocampal-like activity patterns, and used its prediction error as the intrinsic reward to train an Actor-Critic agent. Performance was evaluated using a Novel Object Recognition task to quantify its preference for novel versus familiar stimuli. The RL agent occupied the region of interest (defined as a 3-unit radius around the novel object) significantly more often than a random agent across multiple episodes and novel object locations. The RL agent’s performance was also measured in a multi-room environment, where its visitation frequency to novel rooms was significantly higher than a random control. This work demonstrates that hippocampal-like representations can support autonomous exploratory behaviour, and provides a framework for investigating how cognitive maps guide exploration and navigation.