Students will be involved in genomic, cell based and in vivo projects related to HD:
PROJECT 1: We generated a genome-edited human pluripotent stem c ...
Students will be involved in genomic, cell based and in vivo projects related to HD:
PROJECT 1: We generated a genome-edited human pluripotent stem cell (hPSC) model of HD in which muHTT can be rapidly degraded. The student will learn hPSC biology and look for phenotypes in the presence/absence of HTT. The study is relevant for HTT gene silencing trials. Tutor: Elena Cattaneo & Paola Conforti.
PROJECT 2: The lab has identified new transcription factors (TF) and lncRNA that define striatal neurons formation in the human brain. Genome-editing technologies will be used to overexpress or ablate some these TF in hPSC-derived neurons. Final goal is to make better neurons for cell replacement in HD. Tutor: Elena Cattaneo & Dario Besusso.
PROJECT 3: We have shown that HD mice exhibit a reduction in brain cholesterol biosynthesis, with consequence for disease progression. The project aims to counteract this dysfunction by administering cholesterol-loaded brain-permeable nanoparticles to HD mice. Motor & cognitive tests, molecular and functional assays will define the therapeutic potential of these strategies. Tutor: Marta Valenza.
PROJECT 4: The lab showed that synaptic dysfunction and cognitive decline in HD involve overactive metalloproteinase ADAM10. Our proteomics study also identified ADAM10 interactors at the HD synapse. The student will work with in vivo and ex vivo strategies to dissect the role of ADAM10 and its interactors at the HD cortico-striatal synapse. Tutor: Chiara Zuccato.
PROJECT 5: The lab uses 2D and 3D neuronal differentiation and genome edited lines to test the effect of muHTT and compare it to the human fetal brain. The project includes analyses of data from single cell RNA and ATACseq, bulk RNA seq and Chipseq experiments. Tutor: Elena Cattaneo (with bioinformatics)
