Aditi Methi

This is a test project (1) under the Test Programme.

This project serves as a centralized repository for unpublished omics datasets from ongoing research led by SyNergy group leaders. It includes sample metadata and assay information for studies currently in progress, grouped under investigations such as proteomics and transcriptomics. The project aims to facilitate collaboration and data management within the cluster while maintaining confidentiality for unpublished work.

To explore investigations and their associated studies in more detail, please ...

This project serves as a centralized repository for omics datasets published by research groups within the SyNergy Cluster. It encompasses investigations such as proteomics and transcriptomics, which are further divided into individual studies led by SyNergy members. Each study is linked to relevant publications, assays and data files (with links to external repositories).

To explore investigations and their associated studies in more detail, please visit the 'Related items' tab on the Project ...

Astrocytes play key roles in brain function, but how these are orchestrated by transcription factors (TFs) in the adult brain and aligned with astrocyte heterogeneity is largely unknown. Here we examined the localization and function of the novel astrocyte TF Trps1 (Transcriptional Repressor GATA Binding 1) and the well‐known astrocyte TF Sox9 by Cas9‐mediated deletion using Mokola‐pseudotyped lentiviral delivery into the adult cerebral cortex. Trps1 and Sox9 levels showed heterogeneity among ...

PTEN-induced kinase 1 (PINK1) is a short-lived protein required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane proteins synaptojanin 2 binding ...

Loss-of-function mutations in CLN3 cause juvenile Batten disease, featuring neurodegeneration and early-stage neuroinflammation. How loss of CLN3 function leads to early neuroinflammation is not yet understood. Here, we have comprehensively studied microglia from Cln3∆ex7/8 mice, a genetically accurate disease model. Loss of CLN3 function in microglia leads to lysosomal storage material accumulation and abnormal morphology of subcellular organelles. Moreover, pathological proteomic signatures are ...

Ubiquitin carboxyl-terminal hydrolase 19 (USP19) is a unique deubiquitinase, characterized by multiple variants generated by alternative splicing. Several variants bear a C-terminal transmembrane domain that anchors them to the endoplasmic reticulum. Other than regulating protein stability by preventing proteasome degradation, USP19 has been reported to rescue substrates from endoplasmic reticulum-associated protein degradation in a catalytic-independent manner, promote autophagy, and address ...

Ectodomain shedding, which is the proteolytic release of transmembrane proteins from the cell surface, is crucial for cell-to-cell communication and other biological processes. The metalloproteinase ADAM17 mediates ectodomain shedding of over 50 transmembrane proteins ranging from cytokines and growth factors, such as TNF and EGFR ligands, to signalling receptors and adhesion molecules. Yet, the ADAM17 sheddome is only partly defined and biological functions of the protease have not been fully ...

Astrocytes play key roles in brain function but it is still poorly understood how these are orchestrated by pan-astrocyte transcriptions factors (TFs). Here we examined the function of the well-known pan-astrocyte TF Sox9 and the novel astrocyte TF Trps1 (Transcriptional Repressor GATA Binding 1) by Cas9-mediated in vivo deletion using Mokola-pseudotyped lentiviral delivery into the adult cerebral cortex. The consequences of deleting either Sox9 or Trps1 alone or simultaneously were explored at ...

Astrocyte-specific lentiviral constructs carrying gRNAs targeting Sox9, Trps1 and or both were injected in the cerebral cortex of adult transgenic mice expressing Cas9 protein. Transduced cells were retrived from the cortex 7 and 21 days post injection and subjected to SmartSeq2 for single cell sequencing

PTEN-induced kinase 1 (PINK1) is a very short-lived protein that is required for the removal of damaged mitochondria through Parkin translocation and mitophagy. Because the short half-life of PINK1 limits its ability to be trafficked into neurites, local translation is required for this mitophagy pathway to be active far from the soma. The Pink1 transcript is associated with and cotransported with neuronal mitochondria. In concert with translation, the mitochondrial outer membrane protein ...

The microglial proteome of homozygous Cln3Δex7/8/Δex7/8 was compared with those of littermate control heterozygous (Cln3Δex7/8/+) or wildtype (Cln3+/+) mice at 3 (Cln3Δex7/8/Δex7/8 n=5 vs controls n=7) and 12 months (Cln3Δex7/8/Δex7/8 n=4 vs controls n=5) of age. Microglia were acutely isolated using MACS with CD11b microbeads (Miltenyi Biotec) as previously described in Colombo et al. 36 Sample preparation and mass spectrometric measurements using data independent acquisition were performed as ...

Wild-type (WT) and ADAM17 knockout (KO) mouse embryonic fibroblasts (MEFs) were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM), containing 1% L-Glutamine, 1% Penicilin and Streptomycin, 1% Sodium Pyruvate and 10% Fetal Bovine Serum (FBS) at 37 °C, 5% CO2 (all reagents were purchased from Euroclone, Pero, Italy). HTB94 were kindly provided by Prof Hideaki Nagase, and cultured in DMEM containing 1% L-Glutamine, 1% Penicillin and Streptomycin, 1% Sodium Pyruvate and 10% FBS at 37° C, 5% CO2. ...