Biology subjects

Morris, R. G.

Publications and source records attributed to Morris, R. G..

9 recordsLinked to original sources

bioRxiv2025

Hippocampal reactivation of planned trajectories is required for effective goal choice in an allocentric memory task

Hippocampal activity provides a representation of the world around us, as well as our position within that world. However, it is not known if and to what extent the chosen navigational reference frame can influence hippocampal representations during memory-based tasks, including those focused on future activity. Here, we develop and employ two naturalistic, carefully controlled variants of the everyday memory task to model the use of egocentric and allocentric coordinates in the same arena. By recording hippocampal neural activity through miniature microscopes in male rats performing each of the two tasks, we uncover differences in the representation of space, and in the features of memory-based action planning. By also deploying optogenetic inactivation during navigational decision making, we find that hippocampal representations observed during the planning phase are necessary for solving the allocentric, but not the egocentric version of the task. Overall, our findings reveal a functional link between non-local hippocampal representations and allocentric navigation.

neuroscience↗

bioRxiv2025

Mitochondrial function regulates cell growth kinetics to actively maintain mitochondrial homeostasis

Mitochondria are not produced de novo in newly divided daughter cells, but are inherited from the mother cell during mitosis. While mitochondrial homeostasis is crucial for living cells, the feedback responses that maintain mitochondrial volume across generations of dividing cells remain elusive. Here, using a microfluidic yeast mother machine, we tracked several generations of fission yeast cells and observed that cell size and mitochondrial volume grew exponentially during the cell cycle. We discovered that while mitochondrial homeostasis relied on the sizer mechanism of cell size maintenance, mitochondrial function was a critical determinant of the timing of cell division: cells born with lower than average amounts of mitochondria grew slower and thus added more mitochondria before they divided. Thus, mitochondrial addition during the cell cycle was tailored to the volume of mitochondria at birth, such that all cells ultimately contained the same mitochondrial volume at cell division. Quantitative modelling and experiments with mitochondrial DNA-deficient rho0 cells additionally revealed that mitochondrial function was essential for driving the exponential growth of cells. Taken together, we demonstrate a central role for mitochondrial activity in dictating cellular growth rates and ensuring mitochondrial volume homeostasis.

cell biology↗

bioRxiv2025

Capturing Nematic Order on Tissue Surfaces of Arbitrary Geometry

A leading paradigm for understanding the large-scale behavior of tissues is via generalizations of liquid crystal physics; much like liquid crystals, tissues combine fluid-like, viscoelastic behaviors with local orientational order, such as nematic symmetry. Whilst aspects of quantitative agreement have been achieved for flat monolayers, the most striking features of tissue morphogenesis -- such as symmetry breaking, folding and invagination -- concern surfaces with complex curved geometries. As yet, however, characterizing such complex behaviors in three dimensions has been frustrated due to the absence of proper image analysis methods; current state-of-the-art methods almost exclusively rely on two-dimensional (2D) intensity projections of multiple image planes, which superimpose data and lose geometric information that can be crucial. Here, we describe an analysis pipeline that properly captures the nematic order of tissue surfaces of arbitrary geometry, which we demonstrate in the context of in vitro multicellular aggregates, and in vivo zebrafish hearts. For the former, we correlate the number of topological defects with the aggregates surface area and verify theoretical predictions, whilst for the latter, we link biological properties to physical concepts (Laplace pressure) through spatio-temporal correlations of the heart geometry with fluorescence signals of intracellular proteins. Our analysis enables access to the hidden third dimension of conventional image acquisition via stacked 2D planes and highlights how such characterizations can deliver meaningful physical insight.

biophysics↗

bioRxiv2024

Active morphodynamics of intracellular organelles in the trafficking pathway

From the Golgi apparatus to endosomes, organelles in the endomembrane system exhibit complex and varied morphologies that are often related to their function. Such membrane-bound organelles operate far from equilibrium due to directed fluxes of smaller trafficking vesicles; the physical principles governing the emergence and maintenance of these structures have thus remained elusive. By understanding individual fission and fusion events in terms of active mechano-chemical cycles, we show how such trafficking manifests at the hydrodynamic scale, resulting not only in fluxes of material-- such as membrane area and encapsulated volume-- but also in active stresses that drive momentum transfer between an organelle and its cytosolic environment. Due to the fluid and deformable nature of the bounding membrane, this gives rise to novel physics, coupling nonequilibrium forces to organelle composition, morphology and hydrodynamic flows. We demonstrate how both stable compartment drift and ramified sac-like morphologies, each reminiscent of Golgi-cisternae, emerge naturally from the same underlying nonequilibrium dynamics of fission and fusion.

biophysics↗

bioRxiv2023

Karyopherin mimicry explains how the HIV capsid penetrates nuclear pores

Summary ParagraphHIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus. Remarkably, the intact HIV capsid is over one thousand times greater than the size-limit prescribed by the nuclear pores diffusion barrier. This barrier is a phase-separated condensate in the central channel of the nuclear pore and is comprised of intrinsically-disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG-interactions, cellular karyopherins and their bound cargoes solubilise in this phase to drive nucleocytoplasmic transport. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG-motifs from multiple nucleoporins and that this interaction licenses capsids to penetrate nucleoporin condensates. This karyopherin mimicry model resolves a key conceptual challenge for the role of the HIV capsid in nuclear entry, and explains how an exogenous entity much larger than any known cellular cargo can non-destructively breach the nuclear envelope.

biochemistry↗

bioRxiv2022

Rethinking Population Bottlenecks: Intrinsic Fluctuations, Mutation and Dynamical Demographic Phases

By abruptly changing the size and composition of a population, bottlenecks can dramatically alter evolutionary trajectories. In the traditional picture, the faster a population recovers from a bottleneck, the more rapidly finite-size intrinsic fluctuations are suppressed and therefore the greater the likelihood of fixation to the attractor within whose basin the bottleneck constrained the population, initially. We now argue that this intuition is misleading; demonstrating that precisely the opposite behaviour is also possible. Depending critically on the rate of mutation, increased population growth can drive fixation to attractors that are different to that from whose basin it started. These findings are explained in terms of statistically distinct regimes of demographic behaviour, drawing parallels with the notion of non-equilibrium phase transitions. Such dynamical demographic phases are delimited by sharp transitions in time, as a population grows, and ultimately result from a time-dependent antagonism between mutation and the stochastically-induced effects of frequency-dependent birth.

evolutionary biology↗

bioRxiv2022

Rapid exchange of stably bound protein and DNA cargo on a DNA origami receptor

Biomolecular complexes can form stable assemblies yet can also rapidly exchange their subunits to adapt to environmental changes. Simultaneously allowing for both stability and rapid exchange expands the functional capacity of biomolecular machines and enables continuous function while navigating a complex molecular world. Inspired by biology, we design and synthesize a DNA origami receptor that exploits multi-valent interactions to form stable complexes that are simultaneously capable of rapid subunit exchange. The system utilizes a mechanism first outlined in the context of the DNA replisome, known as multi-site competitive exchange, and achieves a large separation of time scales between spontaneous subunit dissociation, which requires days, and rapid subunit exchange, which occurs in minutes. In addition, we use the DNA origami receptor to demonstrate stable interactions with rapid exchange of both DNA and protein subunits, thus highlighting the applicability of our approach to arbitrary molecular cargo; an important distinction with canonical toehold exchange between single-stranded DNA. We expect this study to be the first of many that use DNA origami structures to exploit multi-valent interactions for the design and synthesis of a wide range of possible kinetic behaviors.

synthetic biology↗

bioRxiv2019

Experience-dependent changes to cortico-hippocampal networks during NREM sleep

Memory reactivation during NonREM-ripples is thought to communicate new information to a systems-wide network. Cortical high frequency events have also been described that co-occur with ripples. Focusing on NonREM sleep after different behaviors, both hippocampal ripples and parietal high frequency oscillations were detected. A bimodal frequency distribution was observed in the parietal high frequency events, faster and slower, with increases in prefrontal directionality measured by Granger causality analysis specifically seen during the fast parietal oscillations. Furthermore, fast events activated prefrontal-parietal cortex whereas slow events activated hippocampal-parietal areas. Finally, there was a learning-induced increase in both number and size of fast high frequency events. These patterns were not seen after novelty exposure or foraging, but occurred after the learning of a new goal location in a maze. Disruption of either sleep or hippocampal ripples impaired long-term memory consistent with these having a role in memory consolidation.

neuroscience↗

bioRxiv2018

Scaffolding of RhoA contractile signaling by anillin: a regulatory analogue of kinetic proofreading

Scaffolding is a fundamental principle of cell signaling commonly thought to involve multi-domain proteins that tether different components of a pathway together into a complex 1,2. We now report an alternative mechanism for scaffolding that is necessary for RhoA-mediated contractile signaling. We find that anillin binding stabilizes active, GTP-RhoA, and promotes contractility at both the epithelial zonula adherens (ZA) and the cytokinetic furrow. However, anillin does not conform to the classical picture of a multi-domain tether, since its RhoA-binding AH domain alone was sufficient to promote contractile signaling. Moreover, anillin competes with contractile effectors for a common site on RhoA, presenting the conundrum of how an inhibitory interaction can otherwise promote signaling. To explain this, we propose that inactivation of RhoA is non-Poissonian, having a rate that increases with time, unless the process is reset via transient binding to anillin. Repeated cycles of binding and un-binding therefore increase cortical residence times of non-sequestered GTP-RhoA and hence the probability of engaging contractile effectors. We identify the modification of the local lipid environment as a potential mechanism underlying such non-Poisson statistics, and demonstrate agreement with a minimal cellular system. Finally, we show that Myosin II anchors anillin at the cortex to form a feedback pathway that enhances RhoA signaling. This new paradigm of scaffolding is a regulatory analogue of kinetic proofreading and may be employed by other binding proteins that do not fit the classical picture.

cell biology↗