Image‐based deep learning reveals the responses of human motor neurons to stress and VCP‐related ALS. C Verzat, J Harley, R Patani, R Luisier. Neuropathology and Applied Neurobiology (2022)
By deploying transfer learning with a pre-trained deep-learning image classifier to a rich multichannel fluorescence microscopy high content imaging data-set, we revealed novel neurite-associated morphological perturbations in ALS disease. This work was done in collaboration with the Patani Lab (Francis Crick Institute, London, Prof. Rickie Patani).
Automated and unbiased discrimination of ALS from control tissue at single cell resolution. C Hagemann, GE Tyzack, DM Taha, H Devine, L Greensmith, J Newcombe, R Patani, A Serio and R Luisier. Brain Pathology (2022)
By combining automated image processing with machine learning methods, we developed a method that enables automatic identification of sick cells with unprecedented accuracy and at single cell resolution in histopathological tissue sections. This work was done in collaboration with the Patani Lab (Francis Crick Institute, London, Prof. Rickie Patani) and the Serio Lab (Kings College, London, Dr Andrea, Serio).
The predicted RNA-binding protein regulome of axonal mRNAs. R Luisier, C Andreassi, LM Fournier, A Riccio. Genome Research (2023).
By integrating 3' end sequencing from cell body and axonal mRNS obtained from rat sympathetic neurons with human CLIP sequencing data, we provide fundamental advances to the current knowledge of post-transcriptional mechanisms that regulate neurotrophin-mediated mRNA metabolism in neurons. This work was done in collaboration with the Riccio Lab (University College London, Prof. Antonella Riccio).
Aberrant cytoplasmic intron retention is a blueprint for RNA binding protein mislocalization in VCP-related amyotrophic lateral sclerosis GE Tyzack, J Neeves, H Crerar, P Klein, O Ziff, DM Taha, R Luisier, N.M. Luscombe, R Patani. Brain (2021).
Physiological intron retaining transcripts in the cytoplasm abound during human motor neurogenesis. MP Howe, H Crerar, J Neeves, J Harley, GE Tyzack, P Klein, A Ramos, R Patani, R Luisier. Genome Research (2022).
These studies show that aberrant cytoplasmic intron retaining transcripts represent a widespread phenomenon in ALS and that these intrinsic sequences exhibit specific features enabling them to create a mislocalization-prone environment for proteins, pointing towards a novel revolutionary role of intronic sequences as regulators of protein localisation, also revealing a potential role for the cytoplasmic intronic sequences in regulating miRNA functionality.