With the emergence of high throughput DNA sequencing technologies, the complete genome sequences of many organisms are deciphered and are being analyzed. Despite the progress, understanding the cellular functions of most of identified genes remains a challenge. The emerging field of “Functional Genomics” aims at providing comprehensive approaches to understand the genome functions, to develop and promote high throughput and large scale approaches to investigate the function of the genomes, their products and the interactions between the two.
Indeed, high-throughput techniques such as high-throughput genome-scale DNA, RNA sequencing or protein analysis by mass spectrometry, are successfully applied to diverse biological questions with the goal of reaching a comprehensive description of their molecular regulation. Yet, they cannot provide temporal or spatial resolution nor directly show that the identified molecules have a function in the dynamic cellular process investigated. Quantitative fluorescence-microscopy in living cells overcomes these limitations because it can probe the function of macromolecules in living cells with ever increasing spatial and temporal resolution.
Imaging-based assays enable genome-wide functional analyses by high-throughput microscopy if combined with standardized reagents that systematically interfere with gene expression or protein activity (e.g. siRNAs, sgRNAs in conjunction with CRISPR/Cas9, chemical inhibitor libraries). In addition, new GFP-tagging genome-editing-based approaches now also allow systematic direct characterization of the abundance, localization, dynamics and interaction of proteins in intact cells, and therefore hold the promise of imaging-based proteomics in single living cells.
This course will provide an overview of the concept of Functional Genomics, how to link a genotype to a phenotype. Contemporary approaches used to understand the genome function will be described and exemplified in this course.
After completing the course, the student will be able to:
- describe what is meant by functional genomics and how this area of research contributes both to new basic biomedical knowledge and to new developments in biomedicine and biotechnology, including improved diagnostics and treatment of disease
- describe and discuss how functional genomics contributes to systems biology and systems medicine
- explain the different state-of-the-art “omics” technologies that are currently applied to perform global analyses at a system level (high throughput transcriptomic and genomic analysis RNA-seq, proteomics and metabolomics)
- explain main principles of bioinformatic tools used for data analysis, biological background knowledge management and modeling
- explain how the researcher can apply high-content screening for functional genomics (RNAi high-throughput screening, high-throughput live cell imaging, high-content imaging systems and tools, high-content image analysis)
Literature will be provided during the course.
Mw. Dr. S. Le Dévédec
Mode of instruction
The course will use a combination of lectures, discussions of assigned literature and computer-based exercises (workshops). Most of the courses will be offered in the morning and will focus on Functional Genomics approaches and their application in (pre-)clinical studies. Students will be expected to critically read assigned papers beforehand. There will also be hands-on experience how bioinformatics tools can be applied to analyze omics and screening data output.
During the course students will perform a computer-based exercise. The course will be concluded by a written exam. Students will be graded for their work in groups (15%) and for the individual written exam (85%).
Admission requirements & Registration
This course is mandatory for and restricted to students who do the Minor ‘Computational approach to Disease Signaling and Drug Targets’ (CADSDT; the entire Minor or only Part 2) or the ‘Elective Module DSDT’. The same admission criteria apply to this course as for the respective afore mentioned programs. Registration for the lectures and exam in uSis is mandatory.