Biology subjects

Fairfax, K. A.

Publications and source records attributed to Fairfax, K. A..

3 recordsLinked to original sources

bioRxiv2025

Identification of Expressed Endogenous Retroviral Element Associated Long Terminal Repeats in Devil Facial Tumour Cells

The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild due to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevents devils from developing devil facial tumour disease would be a major step towards recovering the wild devil population. Critical to an effective DFT vaccine are target antigens. Putative non-coding regions of genomes have been identified as potential tumour-specific antigens for human cancer. These non-coding regions include long terminal repeats of endogenous retroviral elements. We identified 11,193 ERV LTR transcripts that were expressed in DFT1 or DFT2 transcriptomes but not in healthy tissue samples. Using a proteogenomic approach, we identified 33 ERV LTR peptides unique to DFT1 and/or DFT2 immunopeptidomes; four of these were validated in subsequent screens with synthetic peptides. Our study shows the potential for ERV LTRs as novel vaccine targets against DFT1 and DFT2. This method can be applied to other species for the development of cancer vaccine targets that may be shared across tumour types. summaryERV LTRs are present in the Tasmanian devil genome and devil facial tumour cell transcriptomes and immunopeptidome.

cancer biology↗

bioRxiv2025

The impact of sex on the immune system explored at the single-cell level

Sex has a key role in disease susceptibility, in particular autoimmunity. Sex differences of the immune system stems from genes and their interactions with intrinsic and external factors. However, the cellular-level factors influencing sexual dimorphism is not fully understood. We thus examined immune sex differences at single-cell resolution to dissect the genetic impacts. Female-biased sex-differentially expressed genes (DEGs) in multiple immune cells were involved in TNF[a] signalling, whereas male DEGs were enriched for ribosomal-related functions. While cis-eQTLs were less common on sex chromosomes, we identified over 1000 sex-specific eQTLs and 51 sex-interacting eQTLs on autosomes. When we examined the effect of genetic control on sex-DEGs, we found genetic variants affecting the female-biased expression FCGR3A in NK cells (rs2099684) and ITGB2 in Monocytes (rs760462), both of which are associated with systemic lupus erythematosus. Our work reveals novel biases masked in bulk analyses and highlights sexually dimorphic genes and pathways at baseline.

immunology↗

bioRxiv2025

Systematic comparison of Generative AI-Protein Models reveals fundamental differences between structural and sequence-based approaches.

Recent advances in artificial intelligence have led to the development of generative models for de novo protein design. We compared 13 state-of-the-art generative protein models, assessing their ability to produce feasible, diverse, and novel protein monomers. Structural diffusion models generally create designs with higher confidence in predicted structures and more biologically plausible energy distributions, but exhibit limited diversity and strong sequence biases. Conversely, protein language models generate more diverse and novel designs but with lower structural confidence. We also evaluated these models ability to generate unique proteins, conditionally based on the Tobacco Etch Virus (TEV) protease. Generative models were successful in producing functional enzymes, albeit with diminished activity compared to the wildtype TEV. Our systematic benchmarking provides a foundation for evaluating and selecting generative protein models, while highlighting the complementary strengths of different generative paradigms. This framework will facilitate an informed application of these tools for bio-medical engineering and design.

synthetic biology↗