GEM4 Summer School

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Summer 2006: Infectious Disease

The first GEM4 Summer School was held at MIT in Cambridge, Massachusetts in August, 2006, with a focus on the role of biomechanics in infectious disease. Enrollment included 48 students from around the world, with 23 faculty presenting lectures on a variety of topics from basic mechanics and biology to advanced concepts on how mechanics can influence or is reflected in infectious diseases. Classes were held all day, including a collection of intensive laboratory experiences on two afternoons. A high point was a reception at which the students presented posters of their own research and had a chance to sample the wide range of interests of their colleagues. Based on the comments received from participants after the Summer School, it was clear that this two-week session would have significant impact on their future research, and that many valuable ties were made, both with senior faculty and fellow students

Calendar
Lectures
Labs
Photographs

 

Calendar

Day Activities
1 Parallel Tutorial Session 1: Basic mechanics

Parallel Tutorial Session 2: Introduction to physiology

General Tutorial Session 1: Introduction to infectious diseases
2 Parallel Tutorial Session 3: Continuum and statistical mechanics

Parallel Tutorial Session 4: Introduction to molecular biology

Parallel Tutorial Session 5: Introduction to the immune system

Parallel Tutorial Session 6: Cell biology lab
3 Parallel Tutorial Session 7: Molecular mechanics

Parallel Tutorial Session 8: Introduction to cell biology

Laboratories in molecular and cell mechanics
Tissue biomechanics and mechanobiology
Cellular and tissue imaging with multi-photon excitation microscopy
Fast fluorescence microrheology for quantitative studies of cytoskeletal mechanotransduction
Magnetic trap microrheology
4 General Tutorial Session 3: Experimental methods

Laboratories in molecular and cell mechanics
Optical trap; DNA
Optical trap; red blood cells
MEMS; red blood cells
Microfluidics; red blood cells
5 General Tutorial Session 4: Space, time, and energy landscapes mechanobiology

Laboratories in molecular and cell mechanics
AFM/optical trap (hands-on)
AFM; endothelial cells
AFM; force spectroscopy
  Over the weekend:
Review problems, simple homework assignments
Trainees prepare posters to illustrate their own related work, pose research questions
6 Session on connective tissue mechanics

General discussion of dynamics of infectious diseases
7 Session on cell biomechanics

Case studies on inflammation and mechanotransduction

Poster session
8 General Session on molecular biomechanics

Applications and Case Studies
9 Session on Computational Biomechanics

Identification of force-generating element in kinesin motility

Cytoskeleton dynamics simulation of the red blood cell

Multi-scale cell modeling
10 Trainee presentations
Summary and discussion
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Lectures

This page contains documents created from scanned original files, which are inaccessible to screen reader software. A "#" symbol is used to denote such documents.

Day Lectures
1 Parallel Tutorial Session 1: Basic mechanics (PDF - 1 MB)# (student notes)
Simple statistical mechanics for biological systems
Foundations of continuum mechanics

Parallel Tutorial Session 2: Introduction to physiology (PDF - 3.10 MB)# (student notes)

General Tutorial Session 1: Introduction to infectious diseases (PDF)# (student notes)
Human tuberculosis and malaria
The inflammatory cascade (PDF 1) (PDF 2)
Biosafety and laboratory preparedness (PDF - 1.8 MB)
2 Parallel Tutorial Session 3: Continuum and statistical mechanics (PDF)# (student notes)
Simple statistical mechanics for biological systems
Foundations of continuum mechanics; elastic and viscoelastic response

Parallel Tutorial Session 4: Introduction to molecular biology (PDF - 4.2 MB)# (student notes)
Basic concepts in molecular cell biology - the Central Dogma
Control of gene expression

Parallel Tutorial Session 5: Introduction to the immune system (PDF - 1.6 MB)# (student notes)
The immune system of metazoans

Parallel Tutorial Session 6: Cell biology lab
Video show of cell structures, cell adhesion, cell growth and cell motion; laboratory demonstrations of cell culture; basics of light microscopy
3 Parallel Tutorial Session 7: Molecular mechanics (PDF - 3.1 MB)# (student notes)
Basic laws of thermodynamics, generalized force, nonequilibrium statistical mechanics of single molecules (PDF)
The electron problem, classical ion dynamics, molecular dynamics situations

Parallel Tutorial Session 8: Introduction to cell biology (PDF - 1.3 MB)# (student notes)
The cytoskeleton and cell motility
The biology of the red blood cell
4 General Tutorial Session 3: Experimental methods (PDF - 3.1 MB)# (student notes)
Optical tweezers and single-molecule fluorescence methods
AFM imaging and force spectroscopy
Home-built teaching AFM and optical traps
Single and multiple particle tracking methods, magnetic trap (PDF)
3D microscopy -- deconvolution, confocal, 2-photon (PDF)
Micropipette aspiration, other microfluidic methods
MEMS-based tools (PDF)
5 General Tutorial Session 5: Space, time, and energy landscapes mechanobiology (PDF - 1.4 MB)# (student notes)
1) Molecular forces: basic interactions (steric, electrostatic, van der Waals, hydrogen bond, hydrophobic); macromolecular surface forces (electrostatic double layer, DL VO, surface tension); kT as a ruler of molecular forces; self-assembly as a result of competing molecular forces
2) Thermal forces and Brownian motion: random walk picture; meaning of the Central Limit Theorem; diffusion vs. Langevin equation descriptions; diffusion coefficient and fluctuation-dissipation theorem (PDF)
3) Reaction kinetics: Michaelis-Menten kinetics; Arrhenius relation; binding energy/affinity; classical equilibrium picture vs. stochastic picture of rate processes; cooperativity
4) Biological relevance in the context of cell migration, sensing and force generation
6 Session on connective tissue mechanics (PDF)# (student notes)
Elastic and viscoelastic response of connective tissues
Review of basic mechanics
Poroelasticity; Darcy's Law; hydraulic permeability
Tissue mechanics and case studies in human health
Arthritis and joint regeneration
Tendon, ligament, cartilage, bone
Atherosclerosis

General discussion of dynamics of infectious diseases (PDF - 1.4 MB)# (student notes)
Beyond single organism, discuss infection mechanisms and epidemiology/population dynamics
7 Session on cell biomechanics (PDF - 1.3 MB)# (student notes)
Cell membrane mechanics
Cytoskeletal structure and motility
Time dependent responses, CSK mechanics
Cell adhesion, receptor-ligand interaction, focal adhesions
Measurement of cell adhesive forces and kinetics
Microrheology (Mason and Weitz method)
Generalized Stokes-Einstein relationship (GSER)
Nonequilibrium dynamics; evidence for a glassy domain

Case studies on inflammation and mechanotransduction (PDF - 1.7 MB)# (student notes)
Mechanotransduction
Malaria
Asthma
T-cells and immunology from a statistical mechanics perspective
8 General Session on molecular biomechanics (PDF - 4.3 MB)# (student notes)
Brief introduction to molecular biomechanics
Polymer chains, statistics of random walks, persistence length, Boltzmann distribution, freely jointed chain, worm-like chain model (PDF)
Protein conformational dynamics, the role of force in protein-protein interactions
Motor molecules and protein nanomachines
Motility at the macromolecular level, polymerization forces

Applications and Case Studies (PDF)# (student notes)
Case studies on molecular biomechanics and its linkage to infectious diseases
How to decipher the pathogenic processes driven by micro-organisms at the molecular, cellular, and tissue levels
Molecular biomechanics issues in viral replication and viral packaging
Molecular pathways in infectious diseases
Molecular aspects in therapeutics and vaccine design
9

Session on Computational Biomechanics (PDF - 1 MB)# (student notes)
Molecular modeling and simulation
Case studies on continuum modeling and relating it to molecular modeling of mechanosensing proteins
Continuum modeling of the cell

Identification of force-generating element in kinesin motility (PDF - 1.8 MB)# (student notes)

  • Background phenomenology
  • Steered molecular dynamics and force-free simulations
  • Calculating molecular force as a free energy gradient
  • Comparison with experiments

Cytoskeleton dynamics simulation of the red blood cell (PDF - 8.9 MB)

  • Background experiment information
  • A minimal topology evolution model for RBC cytoskeleton
  • Visualization
  • Shearing simulation results
  • Implications for RBC elasticity

Multi-scale cell modeling

10 Trainee presentations
Summary and discussion
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Labs

This page contains documents created from scanned original files, which are inaccessible to screen reader software. A "#" symbol is used to denote such documents.

Lab# Topics
1 Tissue biomechanics and mechanobiology (PDF)
2 Cellular and tissue imaging with multiphoton excitation microscopy (PDF)
3 Fast fluorescence microrheology for quantitative studies of cytoskeletal mechanotransduction (PDF)
4 Magnetic trap microrheology (PDF)
5 Optical trapping and single molecule fluorescence (PDF)
6 Optical tweezers: membrane and cell (PDF)
7 Advanced instrumentation in the teaching lab (PDF)
8 Atomic force microscopy imaging of cells (PDF)
9 Molecular force spectroscopy on living cells (PDF)
10 BioMEMS force sensor (PDF)
11 Microfluidics (PDF)
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2006 Summer School Group Photos

 

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