Technical Courses II: Molecular Biology-Omics 

Description

These series of lectures will provide:

A)      an overview of Next Generation Sequencing (NGS) and the most relevant biomedical NGS applications: Targeted sequencing, Whole-exome sequencing, Whole-genome sequencing, RNA-seq (mRNA-seq, smallRNA-seq, etc., approaches to study RNA structure and RNA-protein interactions), approaches to interrogate the composition and structure of chromatin (ChIP-seq, ATAC-seq, chromosome conformation capture techniques, etc.).

B)      an introduction to proteomic methodologies and their application to the study of human diseases.

C)      an introduction of the significance but also the challenges of applying metabolomic analysis in neurophysiology research. The students will be presented with the major changes in the way problems in life sciences are now approached in the context of the systems biology and the omic analyses revolution, focusing on brain research and the field of systems neurophysiology. The muti-step metabolomic analysis will be described and its contribution to the reconstruction of an accurate metabolic physiology map for the brain will be discussed. Experimental and computational protocol standardization challenges that need to be addressed for its vast deployment in neurophysiology research and practice will be described. An example of brain metabolomic analysis in a mouse model will be presented.

D)      Examples of genetic and biochemical approaches to develop agents interfering with protein aggregation. Many neurodegenerative diseases are associated with protein misfolding and protein self-assembly, which lead to the formation of protein oligomers and/or higher-order aggregates with neurotoxic properties. Thus, understanding these pathogenic processes is of fundamental importance for neurobiology. Furthermore, chemical and biological agents interfering with protein aggregation are much sought-after factors in the quest for effective drugs against these conditions.

Course Overview

The course will cover basic principles of NGS technologies, description of the omic analysis revolution and the consequent fundamental changes in the way problems in life sciences are now approached, mass spectrometry and applications involving differential proteomics, identification of post-translational modifications and analysis of protein complexes as well as of metabolomics. Description of the multi-step experimental and computational analysis process that needs to be carefully designed and standardized for its accurate and vast application in neurophysiology research.

Furthermore, biochemical, biophysical and biological assays, which can be utilized for high-throughput screenings of chemical and biological libraries so as to discover modulators of protein aggregation will be described. Furthermore, the design, development and outcomes of recently developed biotechnological platforms for producing chemical libraries with greatly expanded diversities and for identifying chemical rescuers of pathogenic protein misfolding and aggregation in an ultrahigh-throughput fashion will also be covered. 

Skills & Learning Outcomes

The objective will be to familiarize students with:

1. the principles underlying NGS and the main biomedical applications in which NGS is employed
2. the experimental design of proteomic experiments and current challenges in their application to the study of human diseases.
3. the holistic perspective of biological system analysis gained from systems and network biology research and shown the complementary role of the various omic analyses in deciphering the complexity of brain function
4. metabolomic analysis and it’s various experimental and computational components
5. network reconstruction and how this could contribute to the elucidation of brain metabolic physiology and the reconstruction of the entire brain connectome
6. the experimental and computational challenges that need to be considered for accurate application of metabolomics in brain research
7. state-of-the-art high-throughput approaches for monitoring neurodegeneration-associated protein aggregation and for identifying chemical and biological inhibitors of these processes.
8. recently developed biotechnological approaches for the discovery of chemical rescuers of protein misfolding and aggregation with potentially therapeutic effects against major neurodegenerative diseases.