Molecular Biology and Physiology of the Cell

This programme explores chromatin architecture and its impact on gene expression. It starts with the molecular composition of chromatin, including histones and non-histone proteins, and the structure of the nucleosome. The course delves into epigenetic memory, particularly in early development and centromeric heterochromatin, highlighting the role of histone modifications and pioneer transcription factors. Subsequently, the principles of gene expression control (transcriptional and post-transcriptional) and gene regulatory networks are covered. The molecular mechanisms of cell differentiation and strategies for enhancing cell identity are also investigated. Finally, the programme examines RNA-based gene regulation, the influence of chromatin conformation on gene expression and how chromatin reorganisation orchestrates developmental processes, concluding with state-of-the-art analytical techniques.

Lesson details:

• Lesson 1 - Chromatin Architecture and Epigenetics: Molecular composition of chromatin (histone and non-histone proteins). Nucleosome structure and chromatin folding logic. Nucleosome dynamics and histone chaperones. The role of position effect variegation in Drosophila in discovering epigenetics and genes involved in histone modifications. Histone modification readers and writers, insulators, and heterochromatin spreading. Pioneer transcription factors and early chromatin modifications.
• Lesson 2 - Centromeric Heterochromatin and Epigenetic Memory: Nucleosome organization of centromeric heterochromatin. Mechanisms of epigenetic memory in early development. Genome constancy in vertebrates: nuclear transfer experiments in Xenopus and epigenetic memory in nuclear transplants. Role of Histone H3 isoforms in epigenetic regulation of master developmental genes.
• Lesson 3 - Gene Expression Control: Fundamental principles of gene expression in eukaryotes. Transcriptional and post-transcriptional regulation, analysis of gene regulatory networks, and feedback/feed-forward mechanisms.
• Lesson 4 - Molecular Mechanisms of Cell Differentiation: Genetic processes underlying cellular specialization. Creating expression patterns through gradients and thresholds in Drosophila. Cooperative and combinatorial control of transcription, gene regulatory networks, and regulatory circuits.
• Lesson 5 - Maintenance of Cell Memory: Epigenetic and post-transcriptional mechanisms reinforcing cellular identity. Control of mRNA maturation: splicing and polyadenylation.
• Lesson 6 - RNA-Mediated Gene Regulation: RNA stability and non-coding RNA-mediated regulation. Evolutionary implications of microRNAs in the cerebral cortex and experimental case studies.
• Lesson 7 - Chromatin Conformation and Gene Expression: The role of chromatin in gene regulation. Historical approaches for studying interphase chromatin and modern conformational capture methodologies.
• Lesson 8 - Chromatin Reorganization and Gene Regulation: Interactions between chromatin and the nuclear lamina during cell differentiation. Architectural changes in chromatin during cell commitment and specialization processes.
• Lesson 9 - Chromosome Positioning and Tissue Regulation: Dynamics of chromosome movement and the role of nuclear transmembrane proteins (NETs) in specific chromosome positioning and tissue-regulated gene expression.
• Lesson 10 - Molecular and Cellular Analytical Techniques: Methods for studying gene expression, cell isolation and culture, and molecular and functional analysis applied to biological systems.