Syllabus for The Biogenesis and Cell Biology of Proteins
Time: Second semester
Designed for: undergraduate students (2nd and 3rd year) in biology (3 points - one 2hr lecture a week + tirgul).
Significance:
Every facet of cellular life and function is dependent on the proper biogenesis, directed folding, and vigilant quality control of proteins. Despite their multitude of functions, structures, and electrostatic properties, all proteins have a common feature - the necessity of maintaining "native" structural integrity enabling proper function.
Structure: The introductory part of the course will detail the cellular pathways that ensure correct protein biogenesis, starting from the basic building blocks of amino acids. We will then learn about the significant efforts expended by the cell to maintain protein folding homeostasis over the course of its lifetime. The problematic consequences of protein misfolding, and resultant protein aggregation, will also be discussed; as well as how these processes may contribute to human disease. Finally, the super-structure of protein organization in living cells will be discussed in the context of protein folding and aggregation.
Grades will be assigned based on an exam at the end of the course.
Topics that will be covered include:
Protein Building Blocks – Amino Acids
Functional groups of organic biomolecules
Hydrophobic and Hydrophilic interactions
Condensation and Hydrolysis
The flow of genetic information
The Basis for Protein Folding
The Anfinsen experiment
The Hydrophobic effect
Cysteins and di-sulfide bonds
Exiting the Ribosome
Protein Folding in the Cell
Chaperones and Chaperonins
Post-translational modification
Protein folding in the ER
Molecular crowding
Co-translational folding and degradation
Protein Synthesis and Destruction
The Ubiquitin-Proteasome system
The role of protein degradation in cellular regulation (cell cycle, immune response)
Ubiquitination of misfolded proteins
Chaperones
Chaperone systems: CLiPs and HSPs, Hsp70, Hsp90, Hsp40, Hsp104, sHsps
Chaperones as buffers of function
Protein super-structures and folding together as a heteroligomeric structure
Protein Folding Quality Control
Function of Chaperone systems in Quality Control
Quality Control in Compartments (Cytosol, Nucleus, ER)
Cellular response to protein folding stress
ER stress response
Cytosolic stress response
Oxidative stress
Proteostasis
Global folding and marginal stability
Folding buffers
Aggregation and Inclusions
All proteins can aggregate
Amyloids
Inclusions
Neurodegenerative Diseases
Are inclusions toxic or protective?
Prions
Protein fibers and functional aggregates
Yeast prions
Protective or harmful?
Spatial Organization of Protein Folding Quality Control
The role of compartmentalization in quality control and survival
Techniques for Studying Proteins - Live Cell Imaging
What can imaging do for you?
Why live cell imaging
Molecular dynamics imaging (FRAP, FLIP, FRET, PhAc)
Different approaches in microscopy (Confocality, EM, Spinning Disk, Deconvolution)
Breaking the diffraction limit
Time: Second semester
Designed for: undergraduate students (2nd and 3rd year) in biology (3 points - one 2hr lecture a week + tirgul).
Significance:
Every facet of cellular life and function is dependent on the proper biogenesis, directed folding, and vigilant quality control of proteins. Despite their multitude of functions, structures, and electrostatic properties, all proteins have a common feature - the necessity of maintaining "native" structural integrity enabling proper function.
Structure: The introductory part of the course will detail the cellular pathways that ensure correct protein biogenesis, starting from the basic building blocks of amino acids. We will then learn about the significant efforts expended by the cell to maintain protein folding homeostasis over the course of its lifetime. The problematic consequences of protein misfolding, and resultant protein aggregation, will also be discussed; as well as how these processes may contribute to human disease. Finally, the super-structure of protein organization in living cells will be discussed in the context of protein folding and aggregation.
Grades will be assigned based on an exam at the end of the course.
Topics that will be covered include:
Protein Building Blocks – Amino Acids
Functional groups of organic biomolecules
Hydrophobic and Hydrophilic interactions
Condensation and Hydrolysis
The flow of genetic information
The Basis for Protein Folding
The Anfinsen experiment
The Hydrophobic effect
Cysteins and di-sulfide bonds
Exiting the Ribosome
Protein Folding in the Cell
Chaperones and Chaperonins
Post-translational modification
Protein folding in the ER
Molecular crowding
Co-translational folding and degradation
Protein Synthesis and Destruction
The Ubiquitin-Proteasome system
The role of protein degradation in cellular regulation (cell cycle, immune response)
Ubiquitination of misfolded proteins
Chaperones
Chaperone systems: CLiPs and HSPs, Hsp70, Hsp90, Hsp40, Hsp104, sHsps
Chaperones as buffers of function
Protein super-structures and folding together as a heteroligomeric structure
Protein Folding Quality Control
Function of Chaperone systems in Quality Control
Quality Control in Compartments (Cytosol, Nucleus, ER)
Cellular response to protein folding stress
ER stress response
Cytosolic stress response
Oxidative stress
Proteostasis
Global folding and marginal stability
Folding buffers
Aggregation and Inclusions
All proteins can aggregate
Amyloids
Inclusions
Neurodegenerative Diseases
Are inclusions toxic or protective?
Prions
Protein fibers and functional aggregates
Yeast prions
Protective or harmful?
Spatial Organization of Protein Folding Quality Control
The role of compartmentalization in quality control and survival
Techniques for Studying Proteins - Live Cell Imaging
What can imaging do for you?
Why live cell imaging
Molecular dynamics imaging (FRAP, FLIP, FRET, PhAc)
Different approaches in microscopy (Confocality, EM, Spinning Disk, Deconvolution)
Breaking the diffraction limit
