Biology subjects

Fisher, D.

Publications and source records attributed to Fisher, D..

23 records · Page 2Linked to original sources

bioRxiv2019

Ki-67 supports global gene expression programmes driving tumourigenesis

Recent studies have shown that the cell proliferation antigen Ki-67 is not required for cell proliferation. Here, we demonstrate that Ki-67 enables implementation of transcriptional programmes conferring cellular plasticity, and is required for each step of tumour initiation, growth and metastasis. Ki-67 knockout causes global transcriptome remodelling, which, in mammary carcinoma cells, inhibits the epithelial-mesenchymal transition in a polycomb-repressive complex 2-dependent manner. This results in suppression of stem cell characteristics and sensitisation to various drug classes. Cancer cells lacking Ki-67 proliferate normally in vivo, but tumour growth is inhibited due to disrupted angiogenesis, and metastasis is abrogated. Finally, mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumourigenesis. Thus, Ki-67, which is expressed in all proliferating cancer cells, confers the plasticity required for different steps of carcinogenesis.

cancer biology↗

bioRxiv2019

Predictors of colony extinction vary by habitat type in social spiders

Many animal societies are susceptible to mass mortality events and collapse. Elucidating how environmental pressures determine patterns of collapse is key for our understanding of social evolution. Using the social spider Stegodyphus dumicola we investigated the environmental drivers of colony extinction along two precipitation gradients across southern Africa, using the Namib and Kalahari deserts versus wetter savanna habitats to the north and east. We deployed experimental colonies (n = 242) along two 800km transects and returned to assess colony success in the field after two months. Specifically, we noted colony extinction events after the two-month duration and collected environmental data on the correlates of those extinction events (e.g., evidence of ant attacks, # prey captured). We found that colony extinction events at desert sites were more frequently associated with attacks by predatory ants as compared to savanna sites, while colony extinctions in wetter savannas sites were more tightly associated with fungal outbreaks. Our findings support the hypothesis that environments vary in the selection pressures that they impose on social organisms, which may explain why different social phenotypes are often favored in each habitat.

ecology↗

bioRxiv2018

Dynamic networks of fighting and mating in a wild cricket population

Reproductive success is often highly skewed in animal populations. Yet the processes leading to this are not always clear. Similarly, connections in animal social networks are often non-randomly distributed, with some individuals with many connections and others with few, yet whether there are simple explanations for this pattern has not been determined. Numerous social interactions involve dyads embedded within a wider network. As a result, it may be possible to model which individuals accumulate social interaction through a more general understanding of the social networks structure, and how this structure changes over time. We analysed fighting and mating interactions across the breeding season in a population of wild field crickets under surveillance from a network of video cameras. We fitted stochastic actor-oriented models to determine the dynamic process by which networks of cricket fighting and mating interactions form, and how they co-influence each other. We found crickets tended to fight those in close spatial proximity to them, and those possessing a mutual connection in the fighting network, and heavier crickets fought more often. We also found that crickets who mate with many others tended to fight less in the following time period. This demonstrates that a mixture of spatial constraints, characteristics of individuals and characteristics of the immediate social environment are key for determining social interactions. The mating interaction network required very few parameters to understand its growth and so structure; only homophily by mating success was required to simulate the skew of mating interactions seen in this population. This demonstrates that relatively simple, but dynamic processes can give highly skewed distributions of mating success.

animal behavior and cognition↗

bioRxiv2018

Indirect effects on fitness between individuals that have never met via an extended phenotype

Interactions between organisms are ubiquitous and have important consequences for phenotypes and fitness. Individuals can even influence those they never meet, if they have extended phenotypes which mean the environments others experience are altered. North American red squirrels (Tamiasciurus hudsonicus) guard food hoards, an extended phenotype that typically outlives the individual and is almost always inherited by non relatives. Hoarding by previous owners can therefore influence subsequent owners. We found that red squirrels bred earlier and had higher lifetime fitness if the previous owner was a male. This was driven by hoarding behaviour, as males and mid-aged squirrels had the largest hoards, and these effects persisted across owners, such that if the previous owner was male or died in mid-age subsequent occupants had larger hoards. Individuals can, therefore, influence each others resource dependent traits and fitness without meeting via extended phenotypes, and so the past can influence contemporary population dynamics.

ecology↗

bioRxiv2017

Initiation of DNA replication requires actin dynamics and formin activity

Nuclear actin influences transcription in a manner dependent on its dynamics of polymerisation and nucleocytoplasmic translocation. Using human somatic cells and transcriptionally-silent Xenopus egg extracts, we show that actin dynamics is also required for DNA replication. We identify many actin regulators in replicating nuclei from Xenopus egg extracts, and show that in human cells, nuclear actin filaments form in early G1 and disassemble prior to S-phase. In either system, treatments that stabilise nuclear actin filaments abrogate nuclear transport and initiation of DNA replication. Mechanistically, actin directly binds RanGTP-importin complexes and disruption of its dynamics hinders cargo release. This prevents both nuclear pore complex (NPC) formation and active nuclear transport, which we show is required throughout DNA replication. Nuclear formin activity is required for two further steps: loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin and initiation of DNA replication. Thus, actin dynamics and formins are involved in several nuclear processes essential for cell proliferation.

cell biology↗