Colouring Australia: a participatory open data platform

Colouring Australia is a digital platform for collecting and visualising building level information across several Australian cities. It provides a valuable resource for bringing together data on building age, material, sustainability ratings, walkability and other key metrics as we plan for net zero cities. Colouring Australia comprises part of the international Colouring Cities Research Programme, which supports the development of open-source platforms that provide open data on national building stocks. In this paper we outline the technical architecture of the platform, and the development and visualisation of a building level walkability metric based on pedestrian access to destinations. This platform provides a useful digital tool for planners to understand which parts of the city are walkable and in turn this can support future active transport programs and policies. Future research will be to validate this novel walkability index through a series of stakeholder and public workshops using the Colouring Australia platform in an interactive tabletop environment where usability testing can be undertaken

WalkTHERE

Creating better walkability indice

An animal model of excessive eating: schedule-induced hyperphagia in food-satiated rats.

Nineteen rats were maintained throughout the experiment on ad libitum wet mash and water and were trained to press a lever on fixed-interval or fixed-ratio schedules of reinforcement with electrical brain stimulation. Fourteen rats ate at least 150% more mash during intermittent reinforcement sessions than during baseline, massed reinforcement control, and/or extinction sessions. In a 3-hr session, 11 of those 14 consumed more than 22 g of wet mash (13 g dry weight), the equivalent of nearly half an animal's daily food intake. In subsequent control sessions, the electrodes did not support stimulus-bound eating despite attempts to make stimulation parameters optimal. These results indicate that the eating was schedule induced or adjunctive, and suggest that the procedure may provide an animal model of excessive nonregulatory eating that contributes to obesity in humans

Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis

OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein. DESIGN: We use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair. RESULTS: Targeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not BrafV600E alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting. CONCLUSION: We generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type.status: publishe

Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis

Objective Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated kinase pathway gene, BRAF, and epigenetic modifications termed the CpG Island Methylator Phenotype, leading to epigenetic silencing of key tumour suppressor genes. It is still not clear which (epi-)genetic changes are most important in neoplastic progression and we begin to address this knowledge gap herein.Design We use organoid culture combined with CRISPR/Cas9 genome engineering to sequentially introduce genetic alterations associated with serrated CRC and which regulate the stem cell niche, senescence and DNA mismatch repair.Results Targeted biallelic gene alterations were verified by DNA sequencing. Organoid growth in the absence of niche factors was assessed, as well as analysis of downstream molecular pathway activity. Orthotopic engraftment of complex organoid lines, but not Braf(V600E) alone, quickly generated adenocarcinoma in vivo with serrated features consistent with human disease. Loss of the essential DNA mismatch repair enzyme, Mlh1, led to microsatellite instability. Sphingolipid metabolism genes are differentially regulated in both our mouse models of serrated CRC and human CRC, with key members of this pathway having prognostic significance in the human setting.Conclusion We generate rapid, complex models of serrated CRC to determine the contribution of specific genetic alterations to carcinogenesis. Analysis of our models alongside patient data has led to the identification of a potential susceptibility for this tumour type