(Decoding cancer evolution through the lens of transposable elements and their epigenetic controllers to uncover new diagnostic and therapeutic strategies)
CHALLENGE: Retrotransposable elements
Multidimensional deciphering of how transposable elements and their controllers shape tumour evolution.
The decrypTEd team hopes to define the roles of transposable elements (TEs) and their epigenetic controllers in tumour evolution and use the resulting knowledge to develop novel cancer therapeutics.
TEs and their KRAB zinc finger protein (KZFP) controllers, which bind to and silence repetitive sequences, are major drivers of genome evolution in vertebrates. The team would investigate how TEs and KZFPs are deregulated throughout cancer, focusing on lung, breast and colon cancers and leukaemia, and create the first multi-dimensional single-cell atlas of TEs.
The team would interrogate how TEs drive tumour evolution, perturb specific TE families, characterise KZFPs that are deregulated in cancer and determine the impact of the KZFP-TE system on the tumour environment.
Uniting investigators from the fields of evolutionary biology, cancer genomics, virology, immunology, bioinformatics, mathematics and clinical research, decrypTEd hopes to be able to use the knowledge gained from its investigations to develop therapies targeting the TE and KZFP system.
"Our ambition is to revolutionise our understanding of the human “endovirome” and its epigenetic controllers, by revealing how their sophisticated interplay profoundly influences how tumours can arise, be eliminated or evolve to become life-threatening malignancies, thus unveiling new approaches to fight cancer."