Oscar G. Wilkins

Lysosomal escape and TMEM106B fibrillar core determine TDP-43 seeding outcomes

The paper investigates factors determining TDP-43 seeding outcomes in FTLD-TDP, identifying TMEM106B fibrillar core and lysosomal escape as critical drivers.

Mutual homeostasis of charged proteins

The paper identifies a homeostatic mechanism called interstasis that co-regulates the dosage of proteins with low complexity domains through RNA-based negative feedback.

Characterisation of LAMP1- and LAMP2A-positive organelles in neurons

The paper characterises LAMP1- and LAMP2A-positive organelles in neurons, finding they have distinct transport dynamics and protein compositions.

Creation of de novo cryptic splicing for ALS/FTD precision medicine

The paper develops TDP-REG, a system using cryptic splicing to enable precise gene therapy activation in diseased neurons for ALS/FTD.

Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs

This study shows that loss of TDP-43 causes synaptic dysfunction through a cryptic exon in UNC13A, which is rescued by antisense oligonucleotides.

Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD

The paper shows that loss of TDP-43 function leads to the expression of de novo proteins from mis-spliced mRNA transcripts in ALS/FTD.

TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD

The paper identifies novel cryptic polyadenylation events induced by TDP-43 loss in ALS/FTD using bioinformatic methods and shows their potential disease relevance and impact on protein translation.

Flow: a web platform and open database to analyse, store, curate and share bioinformatics data at scale

Flow provides a web platform and database for managing and analyzing large-scale bioinformatics data, addressing challenges in data processing, quality, and accessibility.

An improved iCLIP protocol

The paper introduces an improved CLIP protocol (iiCLIP) that produces more specific RNA binding site datasets compared to existing methods.

FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation

This study shows that FUS-ALS mutants form cytoplasmic condensates that alter FMRP phase separation, leading to translation inhibition in motor neurons.

Ribocutter: Cas9-mediated rRNA depletion from multiplexed riboseq libraries

The paper introduces a Cas9-based method and software tool to efficiently deplete rRNA/ncRNA contaminants from Ribo-seq libraries, significantly increasing useful reads while minimizing off-target effects.

Common ALS/FTD risk variants in UNC13A exacerbate its cryptic splicing and loss upon TDP-43 mislocalization

The paper shows that ALS/FTD risk variants in UNC13A increase sensitivity to TDP-43 depletion by promoting cryptic exon inclusion and protein loss.