Evolution of genomic and transcriptomic susceptibilities to cancer across mammals
Supervisors
Manuel Irimia
CRG, 1st supervisor
Nuno Morais
GIMM, 2nd supervisor
Objectives
Cancer arises from somatic mutations in specific genes, leading to both genomic changes and characteristic transcriptomic alterations in tumours. Interestingly, cancer incidence does not correlate with body size or lifespan across species, a phenomenon known as Peto’s paradox. This suggests that some species have evolved molecular mechanisms that protect against cancer. This project aims to investigate these mechanisms by analysing cancer-related genomic and transcriptomic «susceptibilities» across mammalian species. In particular, we will evaluate transcriptomic cancer signatures (gene expression and splicing) across species, deriving a cancer susceptibility score based on how closely each species’ transcriptome resembles cancer profiles. In addition, we will investigate how these and other transcriptomic signatures contribute to the origin and evolution of cancer types, analogously to the evolution of physiological cell types.
Methodology
We will evaluate transcriptomic cancer signatures of gene expression and alternative splicing across species. For this, the DC will process bulk and single-cell data from multiple species and tissues and will derive and validate various cancer and age-related signatures. In a second step, genome adaptations in protein-coding sequences and regulatory regions behind those transcriptomic adaptations will be identified.
Required Skills
Bioinformatician with experience in transcriptomic analyses, and ideally comparative omics. A curious mind, willing to try their own ideas and a high collaborative spirit.
Expected Results
We expect to identify lower expression of transcriptomic cancer signatures (Aim 1) in species with large body sizes and long lifespans. In addition, we will identify transcriptomic signatures that contribute to the origin and evolution of cancer types (Aim 2). These insights will contribute to understanding evolutionary adaptations to cancer prevention and could reveal novel protective mechanisms that may be relevant to human health.
Planned Secondments
GIMM (Morais) in year 2 (1.5 months) to receive training on software for high-level transcriptomic analyses and statistical methods.
ICR (Graham) in year 3 (1 month) to learn about research on adaptive therapies and tumour drug resistance evolution.
IP (Berthelot) in year 3 (2 weeks) to learn about epigenomics and GWAS.
Enrolment in doctoral programs
PhD in Biomedicine from Universitat Pompeu Fabra
References
Mantica, F., Iñiguez, L.P., Marquez, Y., Permanyer, J., Torres-Mendez, A., Cruz, J., Franch-Marro, X., Tulenko, F., Burguera, D., Bertrand, S., Doyle, T., Nouzova, M., Currie, P., Noriega, F.G., Escriva, H., Arnone, M.I., Albertin, C.B., Wotton, K.R., Almudi, I., Martin, D., Irimia, M. (2024). Evolution of tissue-specific expression of ancestral genes across vertebrates and insects. Nature Ecol Evol, 8(6):1140-1153.