We are looking for a motivated PhD student to join our project "Social Cognition In Silico and In Vivo" (SCIVIS), with proficiency in Dutch of at least B2 level. The research is embedded in a vibrant and interdisciplinary research network. The Center Neuropsychiatry at KU Leuven (Belgium) operates at the crossroads of neurology, psychiatry, and cognitive neuroscience. Through an integrated, interdisciplinary approach, we investigate how brain networks support behavior, emotions, and social interaction, both in neurotypical individuals and in people with neuropsychiatric conditions. The project is conducted in close collaboration with the Research Unit Brain & Cognition at KU Leuven, known for its expertise in experimental psychology and cognitive neuroscience, and the AI Lab of VUB university, Brussels, a leading center in artificial intelligence research. Together, these partners bring complementary strengths to the study of social cognition, linking brain, behavior, and computation. As part of the SCIVIS project, we are looking for a PhD candidate to investigate the neural underpinnings of social cognition using functional brain imaging (fMRI/fNIRS). This cutting-edge initiative bridges neuroscience and artificial intelligence to advance our understanding of social cognition in both neurotypical individuals and those with atypical development, with a particular focus on autism and frontotemporal dementia. The position offers the opportunity to design and carry out behavioral and neuroimaging experiments, and to collaborate closely with computational scientists and experimental psychologists. You will join a dynamic research team and contribute to high-impact science at the interface of neuroscience and AI, with real potential to advance our understanding of the social brain. As a PhD student, you will contribute mostly to the in vivo research package, including: Designing and conducting behavioral and neuroimaging experiments (fMRI and fNIRS) to explore social cognitive functions. Collecting and analyzing imaging data to investigate the brain mechanisms underlying social cognition. Collaborating with a multidisciplinary team and integrating findings with computational modeling efforts. Preparing publications for leading scientific journals and presenting at international conferences.

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wide association studies, but how those variants increase risk for disease is unknown. We discovered that TDP-43 represses a cryptic exon-splicing event in UNC13A. Loss of TDP-43 from the nucleus in human brain, neuronal cell lines and motor neurons derived from induced pluripotent stem cells resulted in the inclusion of a cryptic exon in UNC13A mRNA and reduced UNC13A protein expression. The top variants associated with FTD or ALS risk in humans are located in the intron harboring the cryptic exon, and we show that they increase UNC13A cryptic exon splicing in the face of TDP-43 dysfunction. Together, our data provide a direct functional link between one of the strongest genetic risk factors for FTD and ALS (UNC13A genetic variants), and loss of TDP-43 function. Recent analyses have revealed even further changes in TDP-43 target genes, including widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., ELP1, NEFL, and TMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.

The development of human induced pluripotent stem cells (iPSC) and their subsequent differentiation into neurons has provided new opportunities for the generation of physiologically-relevant, in vitro disease models. I will present our work using iPSC to modal familial Alzheimer's Disease (fAD) and Frontotemporal Dementia (FTD). We have investigated the mutation-specific effects of APP and PSEN1 mutations on Abeta generation in neurons generated from individuals with fAD, revealing distinct mechanisms that may contribute to clinical heterogeneity in disease. I will also discuss our work to understand the developmental and pathological changes to tau that occur in iPSC-neurons, particularly the challenges of understanding tau pathology in a developmental system, tau proteostasis and how iPSC-neurons may help us identify early signatures of tau pathology in disease.