Biology subjects

Perry, K. D.

Publications and source records attributed to Perry, K. D..

3 recordsLinked to original sources

bioRxiv2025

An immunocompetent mouse model of liposarcoma

Liposarcoma (LPS) is the most prevalent soft tissue sarcoma. The most common biological subtypes are well-differentiated (WDLPS), a low-grade disease that can evolve to high-grade dedifferentiated liposarcoma (DDLPS), with increased rates of recurrence and metastasis and low response rates to systemic therapies. Preclinical testing of immunotherapeutics for LPS has been held back by the lack of an immunocompetent mouse model. Here, we present an autochthonous immunocompetent LPS mouse model, ACPP, with targeted deletion of Trp53 and Pten in adipocytes to mimic signaling alterations observed in human LPS. Similar to humans, ACPP mice produce WDLPS, DDLPS, and tumors that exhibit both WD and DD components. Murine and human DDLPS tumors possess transcriptional similarities, including increased expression of oncogenes Cdk4 and Hmga2 and reduced expression of the tumor suppressor Cebpa; furthermore, both mouse and human DDLPS exhibit heterogenous T cell infiltration. Syngeneic cell lines derived from ACPP DDLPS reliably produce tumors following orthotopic implantation, each with distinct growth patterns, aggressiveness, and immune profiles. These unique models provide much needed tools to understand the complex immunobiology of LPS and greatly accelerate the pace of preclinical studies aimed at uncovering more effective new therapies for patients with this aggressive malignancy.

cancer biology↗

bioRxiv2017

A global Brassica pest and a sympatric cryptic ally, Plutella australiana (Lepidoptera: Plutellidae), show strong divergence despite the capacity to hybridize

The diamondback moth, Plutella xylostella, has been intensively studied due to its ability to evolve insecticide resistance and status as the worlds most destructive pest of brassicaceous crops. The surprise discovery of a cryptic ally, Plutella australiana Landry & Hebert, with apparent endemism to Australia, immediately raised questions regarding the extent of ecological and genetic diversity between these two species, whether gene flow could occur, and ultimately if specific management was required. Here, we show that despite sympatric distributions and the capacity to hybridize in controlled laboratory experiments, striking differences in genetic and phenotypic traits exist that are consistent with contrasting colonization histories and reproductive isolation after secondary contact. Almost 1500 Plutella individuals were collected from wild and cultivated brassicaceous plants at 75 locations throughout Australia. Plutella australiana was commonly found on all Brassica host types sampled except commercial vegetables, which are routinely sprayed with insecticide. Bioassays using four commonly-used insecticides found that P. australiana was 19-306 fold more susceptible than P. xylostella. Genome-wide SNPs derived from RADseq revealed substantially higher levels of genetic diversity across P. australiana compared with P. xylostella nuclear genomes, yet both species showed limited variation in mtDNA. Infection with a single Wolbachia subgroup B strain was fixed in P. australiana, suggesting that a selective sweep contributed to low mtDNA diversity, while a subgroup A strain infected just 1.5 % of P. xylostella. Although P. australiana is a potential pest of brassica crops, it is of secondary importance to P. xylostella.

genetics↗

bioRxiv2017

Genome-Wide SNP Discovery In Field And Laboratory Colonies Of Australian Plutella Species

Understanding dispersal and gene flow is an important focus of evolutionary biology, conservation biology and pest management. The diamondback moth, Plutella xylostella, is a worldwide pest of Brassica vegetable and oilseed cropping systems. This insect has high dispersal ability, which has important consequences for population dynamics and the potential spread of insecticide resistance genes. Population genetic studies of the diamondback moth have found little evidence of population structure, suggesting that frequent intermixing occurs within regions, however the patterns of local and regional dispersal remain to be identified. For this and many other pest species, understanding dispersal is crucial for developing integrated management tactics such as forecasting systems and insecticide resistance management plans. In recent years, next generation sequencing (NGS) methods have provided previously unparalleled resolution for population genetic studies in a wide range of species. Here, we assessed the potential of NGS-derived molecular markers to provide new insights about population structure in the diamondback moth. We use restriction-site-associated DNA sequencing (RAD-Seq) to discover hundreds to thousands of single nucleotide polymorphism (SNP) markers in nine field and laboratory-reared populations collected from Australia. Genotypic data from RAD-Seq markers identified a cryptic species, P. australiana, among individuals collected from a wild host, Diplotaxis sp., indicating strong divergence in the nuclear genomes of two Australian Plutella lineages. Significant genetic differentiation was detected among populations of P. xylostella used in our study, however this could be explained by reduced heterozogosity and genetic drift in laboratory-reared populations founded by relatively few individuals. This study demonstrates that RAD-Seq is a powerful method for generating SNP markers for population genetic studies in this species.

ecology↗