L1-EGFP positive cortical neuron (GFP in green, MAP2 – neuronal marker in magenta, nuclei in blue)

Lay summary of research
Mobile DNA, or “jumping genes” are pieces of DNA that can copy-and-paste, or cut-and-paste, themselves from one part of a genome (the genetic instructions for an organism) to another part of the same genome. Mobile DNA is found in virtually all multicellular organisms and is particularly common in the genomes of animals and plants. Because of mobile DNA’s need to copy itself to survive and propagate over time, it can generate DNA sequences that are repeated over and over again in a genome. This repetitiveness can make mobile DNA difficult to study, and has led to mobile DNA being at times overlooked in the modern era of “genomics”, where DNA sequencing is used across a broad spectrum of biological and biomedical research. Our research is aimed at finding key examples of mobile DNA impacting human health, emphasising roles it may play in the brain (e.g. memory formation, dementia), cancer, embryo development and female fertility. 

Scientific summary of our research
Our laboratory is particularly interested in a type of mobile genetic element called Long Interspersed Element 1 (LINE-1 or L1). L1 occupies ~17% of the human genome and spreads via a ‘copy and paste’ mechanism called retrotransposition. New L1 insertions can profoundly alter gene structure and expression, and cause disease. L1 uses a 6kb mRNA encoding two proteins, ORF1p and ORF2p, to retrotranspose. A typical L1 insertion involves a degenerate L1 endonuclease recognition motif, an L1 poly-A tail and, crucially, yields target site duplications (TSDs). These hallmarks of target primed reverse transcription (TPRT) distinguish L1 insertions from genome structural rearrangements and molecular artefacts. Germline retrotransposition is an established paradigm in animals. However, recent work has shown that L1 can also mobilise during embryogenesis, in neurons, and in other somatic cells. The extent and consequences of endogenous L1 retrotransposition in human tissues are almost entirely unexplored. Our main research objective is to define the spatiotemporal extent and biological impact of L1 mobilisation in normal and diseased cells, with an emphasis on the early embryo, brain, and cancer. To this end, we employ a number of cutting-edge approaches, including single-cell genomics, whole-genome sequencing, bioinformatics, transgenic systems and genome editing. 


Further reading

Geoffrey J Faulkner, Jose L Garcia-Perez: L1 Mosaicism in Mammals: Extent, Effects, and Evolution. In: Trends Genet., 33 (11), pp. 802–816, 2017.
Sandra R Richardson, Santiago Morell, Geoffrey J Faulkner: L1 retrotransposons and somatic mosaicism in the brain. In: Annu. Rev. Genet., 48 , pp. 1–27, 2014.
Patricia E Carreira, Sandra R Richardson, Geoffrey J Faulkner: L1 retrotransposons, cancer stem cells and oncogenesis. In: FEBS J., 281 (1), pp. 63–73, 2014.
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