4S03
Molecular Biophysics - 2014
Dr Paul Higgs
Schedule for Fall 2014: Mo
We Th 10.30, UH/B116
Course Aims
The course will focus on
the single-molecule approach to biophysics experiments. Students will learn to
appreciate methods for observing and manipulating single molecules and what can
be understood with these techniques about the structure, function and dynamics
of biological molecules. Ideas from thermodynamics and soft-matter physics will
be used to explain the observations and make predictions about the behaviour of
the biological molecules. Students should appreciate the interdisciplinary
nature of the subject – physics/biochemistry/biology – and the interplay between
theory and measurements. Lectures will make use of example papers from the
scientific literature for each of the topics considered. Students will gain
practice in reading and interpreting the primary literature in the field.
Lecture Contents
Techniques for observing
and manipulating molecules, including optical tweezers, atomic force microscopy
and fluorescence methods.
Force-extension curves for
DNA, proteins and RNA.
DNA structure and packaging
(nucleosomes, viruses).
Helix-coil transitions in
nucleic acids and proteins.
Folding of RNA and Proteins
– observations and thermodynamic models.
Assembly and growth of
microtubules and actin filaments.
Molecular Motors (myosin, kinesin, ATP synthase, flagellar motor)
Assignments
There will be 3 assignments
based on interpretation of papers in the biophysics field (worth 15% each).
Assignments will be downloadable from this web site. Due dates will be
announced when the assignment is issued. A printed version of the completed
assignment should be handed in at the lecture on the due date.
There will be a mid-term
test (worth 15%) and a final exam (worth 40%). The mid-term will be based on
all topics covered up to that point and the final exam will be based on all
topics covered in the course. The format of the exam questions will be
discussed with the class prior to the exam.
Assignment 1 - Assignment 1.doc You will need the following
paper for this assignment - ForceExtRNA_Liphardt2001.pdf
- DEADLINE Mon 29th Sept
Assignment 2 - Assignment2.doc You will need the following paper - Microtubules_Fygensen.pdf - DEADLINE
CHANGED to Wed 29th Oct.
LECTURE CANCELLED on Mon
27th because of CUPC conference. Also no lecture on Thur
30th because of Recess.
Midterm - Mon 3rd Nov -
Examples of past midterm exams : Midterm2013 Midterm2010
Assignment 3 - You will need the following
paper for the written part - Betancourt
.
DEADLINE: Everyone -
Written Part of Assignment 3 - Mon 24th Nov.
DEADLINE: Grad students -
Review of 10 papers - Wed 3rd Dec (= last lecture)
Presentation Dates
Mon Nov 17th - Alex and
Chapin - Guolla - Force transduction and strain dynamics of actin in stress fibres in response to nanonewton
forces
Wed Nov 19th - Sean and
Eric - Blanchard - tRNA
selection and kinetic proofreading in translation
Thur Nov 20th - Andrew A and Ashley - Moerner - Single
molecule spectroscopy and imaging of biomolecules in
living cells
Mon Nov 24th - Michael - Zimmerberg
- How proteins produce cellular membrane curvature
Wed Nov 26th - Dennis and
Andrew W - Attwater
- In-ice evolution of RNA polymerase ribozyme activity
Thur Nov 27th - Adam - Viscek - A novel
type of phase transition in a system of self-driven particles
Recommended Textbook
Rob Phillips, Jane Kondev, Julie Theriot (2009) The
Physical Biology of the Cell – This is a textbook covering many biological
problems from a physics point of view. Lectures will refer to this book where
appropriate, but will also use a lot of material from other research papers.
Background Reading
For those who are not
familiar with Biochemistry - I would like you to have a general idea of the structure of the
important types of biological macromolecules (proteins, DNA, RNA, lipids, polysaccharides)
and the roles played by these molecules in the cell. There are many textbooks
on this, but for something that is at the right level and not too long, I would
recommend Chapter 5, "The structure and function of macromolecules",
from the book "Biology" by N A Campbell and J B Reece. This should be
in the library, and I have one copy that can be borrowed.
For everyone - Look at Chapters 1 and 2 of
Phillips et al. This covers some ideas on sizes of molecules and cells that we
talked about in class, and gives a physicist's point of view on the importance
of models in biology.
The instructor and
university reserve the right to modify elements of the course during the term.
The university may change the dates and deadlines for any or all courses in
extreme circumstances. If either type of modification becomes necessary,
reasonable notice and communication with the students will be given with
explanation and the opportunity to comment on changes. It is the responsibility
of the student to check their McMaster email and course websites weekly during
the term and to note any changes.
Stuff to Download
Pictures from Phillips –
Sizes and Time Scales - Notes1
Papers on Optical Tweezers
– Review of Scientific Instruments Neuman and Block – Calibration using Power Spectrum BergSorensen
Pictures related to DNA
force-extension experiments and DNA-histone interactions - Notes2
Papers on DNA
force-extension experiments - Bustamante2000 Bustamante2003
Physics of Chromatin Review
Schiessel2003 . Simulation of
charged chain and sphere Kunze2000
Papers on nucleosomes that
we mentioned in lectures: Schiessel2006.pdf
, BrowerToland.pdf , Mihardja2006.pdf
Helix-Coil Notes : Notes1 and Notes2
RNA folding : RNANotes - QRBHiggs2000.pdf
Movie Links are here.
Netlogo program
for dynamic instability of microtubules.
CATH database
PDB database
Papers on Protein Folding -
ProteinFolding_Dill.pdf - ProteinFolding_Sali.pdf - ProteinFolding_Beck.pdf
Notes - Fluorescence Techniques
More stuff as we go
along.....