Research Group Proteostasis (Dr. Mateusz C. Ambrozkiewicz)
The research group investigates how regulation of protein status, i.e. specific ways of protein synthesis and folding as well as defined degradation pathways orchestrate cortical development.
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Summary of work program
From an evolutionary perspective, the cerebral cortex represents the most recent development in our brain and serves as the biological foundation for our cognitive abilities. One of the prominent features of the cerebral cortex is the remarkable diversity of its cell types. Generated from progenitor cells, glutamatergic neurons can be further subdivided based on the transcriptional signatures, electrophysiological properties, and connectivity patterns. For decades, unravelling the molecular factors driving this cellular diversification in the neocortex has remained a central focus in developmental neuroscience. In recent years, we have observed excellent research works, delineating the transcriptomes of single cells in the mammalian cortex, generating comprehensive maps and atlases of cellular states and differentiation trajectories. In our previous research, we investigated molecular cascades that go beyond transcription, shedding light on the crucial roles of protein translation and ubiquitination-mediated degradation.
https://fenskavlinetwork.org/portfolio/mateusz-ambrozkiewicz/
Our interests
Currently in our group, we investigate the establishment of cellular diversity in the cortex during development. Specifically, we study the regulation of the proteome, i.e. the protein modifications by ubiquitin and ubiquitin-like modifiers and their consequences for the developing cortex. Our research can be divided into three main objectives: 1) generation of a molecular map of protein degradation at a cellular resolution in the developing cortex; 2) investigation of the connection between protein structure and function in the brain by decoding the involvement of E3 ubiquitin ligases in the etiology of human neurodevelopmental disorders; 3) studies on functional consequences of proteome modifications, such as ufmylation in the developing neuronal lineages. In our research, we use in utero electroporation, animal genetics, cell and slice cultures, a broad range of microscopy techniques (apart from standard confocal, light sheet and expansion microscopy), state-of-the-art biochemical assays and high-throughput mass spectrometry.