bioRxiv ScienceSearch

Biology subjects

McCann, C.

Publications and source records attributed to McCann, C..

2 recordsLinked to original sources

A mechanistic hydro-epidemiological model of liver fluke risk

The majority of existing models for predicting disease risk in response to climate change are empirical. These models exploit correlations between historical data, rather than explicitly describing relationships between cause and response variables. Therefore, they are unsuitable for capturing impacts beyond historically observed variability and cannot be employed to assess interventions. In this study, we integrate environmental and epidemiological processes into a new mechanistic model, taking the widespread parasitic disease of fasciolosis as an example. The model simulates environmental suitability for disease transmission, explicitly linking the parasite life-cycle to key weather-water-environment conditions. First, using epidemiological data, we show that the model can reproduce observed infection levels in time and space over two case studies in the UK. Second, to overcome data limitations, we propose a calibration approach based on Monte Carlo sampling and expert opinion, which allows constraint of the model in a process-based way, including a quantification of uncertainty. Finally, comparison with information from the literature and a widely-used empirical risk index shows that the simulated disease dynamics agree with what has been traditionally observed, and that the new model gives better insight into the time-space patterns of infection, which will be valuable for decision support.

epidemiology

Modulation of Genome Editing Outcomes by Cell Cycle Control of Cas9 Expression

Targeting specific chromosomal sequences for genome modification or regulation during particular phases of the cell cycle may prove useful in creating more precise, predictable genetic changes. Here, we present a system using a fusion protein comprised of a programmable DNA modification protein, Cas9, linked to a cell cycle regulated protein, geminin, as well as green fluorescent protein (GFP) for visualization. Despite the large size of Cas9 relative to geminin, cells were observed to express Cas9-GFP-geminin at levels which oscillate with the cell cycle. These fusion proteins are also shown to retain double-strand break (DSB) activity at specific chromosomal sequences to produce both indels and targeted integration of donor ssDNA. Most importantly, the ratio of ssDNA donor integration to non-homologous end joining (NHEJ) was observed to increase, suggesting that cell cycle control Cas9 expression may be an effective strategy to bias DNA repair outcomes.

molecular biology