Biology subjects

Larson, A. G.

Publications and source records attributed to Larson, A. G..

4 recordsLinked to original sources

bioRxiv2026

Survival Benefits Outweigh Germline Competition Costs in Kin Chimeras

Chimerism, the coexistence of genetically distinct cells within an organism, is a widespread phenomenon in nature. In the colonial chordate Botryllus schlosseri, fusion between compatible colonies can lead to stem cell competition with a single genotype taking over the gonadal and/or somatic tissue of the chimera. Over five years, we quantified the frequency and consequences of chimeric formation among 809 larvae, assessing the rates of fusion after natural settlement and its long-term impact on colony survival. We found larvae preferentially settle near kin, facilitating high rates of successful fusion. Fusion was concentrated around the first month of life, boosting survival during this period of high mortality. At all timepoints chimerism significantly increased survival relative to naive and rejected colonies and extended overall lifespan. However, fusion triggered intense internal competition: in all cases tested, a single genotype achieved dominance over both germline and somatic tissues within several weeks post-fusion, regardless of initial genotype contribution. We estimate that among kin, the survival benefits of chimerism outweigh the potential costs of germline loss, extending Hamiltons kin selection framework to colonial marine organisms. In this context, chimerism functions as an adaptive strategy that enhances early survival while enabling selection among competing stem cell lineages.

evolutionary biology↗

bioRxiv2024

Chromatin mimicry by human JC virus

Chronically persistent viruses are integral components of the organismal ecosystem in humans and animals 1 2. Many of these viruses replicate and accumulate within the cell nucleus 3. The nuclear location allows viruses to evade cytoplasmic host viral sensors and promotes viral replication 4. One of the unexplored and puzzling aspects of the viral nuclear lifecycle involves the viruss ability to deal with the physical constraints of nuclear architecture. To replicate and accumulate within the nucleus in large numbers sufficient for infection spreading, DNA viruses need to overcome the spatial limitations imposed by chromatin and the nuclear matrix. We found that one of the most widespread and potentially lethal human viruses, the JC polyomavirus 5, interferes with nuclear heterochromatin to create virus-occupied space. The JC viruss impact on heterochromatin is mediated by the viral nonstructural protein, Agnoprotein (Agno). Agnos interference with heterochromatin is governed by structurally diverse mimics of host epigenetic regulators that facilitate virus-induced chromatin reorganization and a dramatic decline in nuclear stiffness in the infected cells. The JCV epigenetic mimicry is critical for the virus infection, as evident from reduced replication of mimic-mutant viruses. Our data suggest that modulation of nuclear mechanical properties is a novel strategy enabling chronicity of the JC and possibly other nuclear virus infections.

microbiology↗

bioRxiv2022

A topologically complex cytoplasm enables inflation-based escape from a gravity trap

The daily vertical migrations of plankton play a crucial role in shaping marine ecosystems and influencing global biogeochemical cycles. They also form the foundation of the largest daily biomass movement on Earth. Surprisingly, amongst this diverse group of organisms, some single cell protists transit these depths exceeding 50 meters without employing flagella or cilia, and the underlying mechanisms remain poorly understood. It has been previously proposed that this capability relies on the cells ability to regulate its internal density relative to seawater. Here, using Pyrocystis noctiluca as a model system, we demonstrate the primary mechanism for this density control is a rapid cellular inflation event, during which a single plankton cell expands its volume six-fold in less than 10 minutes. This self-regulated cellular inflation selectively imports fluid less dense than surrounding seawater, and can effectively sling-shot a cell and reverse sedimentation within minutes. This ability is made possible by a reticulated cytoplasmic architecture in Pyrocystis noctiluca that enables this rapid increase in overall cell volume without dilution of its cytoplasmic content. We further present a generalized mathematical framework that unifies cell cycle driven density regulation, stratified ecology, and associated cell behavior in the open ocean. Our study unveils an ingenious strategy employed by non-motile plankton to evade the gravitational sedimentation trap, highlighting how precise control of cell size was essential for survival in the ocean.

cell biology↗

bioRxiv2020

Cryo-EM analysis of human mitochondrial Hsp90 in multiple tetrameric states

Hsp90 is a ubiquitous molecular chaperone that mediates the folding and maturation of hundreds of "client" proteins. Although Hsp90s generally function as homodimers, recent discoveries suggested that the mitochondrion specific Hsp90 (TRAP1) also forms functionally relevant tetramers. The structural mechanism of tetramer formation remains elusive. Here we used a combination of solution, biochemical and cryo-electron microscopy (cryo-EM) approaches to confirm that, independent of nucleotide state, a subpopulation of TRAP1 exists as tetramers. Unexpectedly, cryo-EM reveals multiple tetramer conformations having TRAP1 dimers arranged in orthogonal, parallel, or antiparallel configurations. The cryo-EM structure of one of the orthogonal tetrameric states was determined at 3.5 [A] resolution. Each of the two TRAP1 dimers is in a symmetric AMP{middle dot}PNP-bound closed state with the tetramer being stabilized through three distinct dimer-dimer interaction sites. In unique ways, each of the three TRAP1 domains contributes to tetramer formation. In addition to tetramerization via direct dimer-dimer contacts, our structure suggests that additional stabilization could come from domain swapping between the dimers. These results expand our understanding of TRAP1 biology beyond the conventional view of a functional dimer and provide a platform to further explore the function and regulation of tetrameric TRAP1 in mitochondria.

biophysics↗