4S03
Molecular Biophysics - 2010
Dr Paul Higgs
Schedule for Fall 2010:
Tue, Wed, Fri 9.30 CNH217
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.
Graduate students taking
6S03 will also carry out a literature survey to be arranged separately with Dr
Higgs.
Assignment 1 - Assignment 1.pdf You will need the following paper for this
assignment - ForceExtRNA_Liphardt2001.pdf
– Due date Wed 6th October.
Assignment 2 - Assignment2.doc You will need the following paper for this
assignment - Microtubules_Dogterom.pdf
– Due date Wed 27th October.
Midterm will be in the
lecture room on Tue Nov 9th
Assignment 3 - Assignment3.doc You will need the following two papers for
this assignment - GroEL_Betancourt.pdf
and DAMs_Subramanian.pdf – Due date Wed
24th November.
Useful Books
Alex E Knight (2009) Single
Molecule Biology – This is a book of review articles covering many of the
topics on the course. Lectures will draw on examples from this book. However,
this is not a specific 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.
We will not follow either
book specifically. Papers from the primary literature will be posted on this
web site for study. Lectures will focus on explanation of the methods and
results in these chosen papers.
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
(we looked at section 2.3 in particular) Schiessel2003 . Simulation of
charged chain and sphere Kunze2000
Papers on nucleosomes that we mentioned in lectures: Schiessel2006.pdf , BrowerToland.pdf , Mihardja2006.pdf
More information on Helix-Coil transitions.
Good textbook – Cantor and Schimmel.
Biophysical Chemistry Part III (Chapter 20)
- QH345.C36v3
Specialized book – D. Poland (1970) Theory of Helix-coil transitions in
biopolymers – QD381.P6
Helix coil transparencies (thanks to Chris Kim): HelixCoil_Notes1.pdf and HelixCoil_Notes2.pdf
Review paper on RNA secondary structure QRBHiggs2000.pdf
Lecture notes on RNA RNANotes.ppt
Paper using RNA sequences to construct mammalian phylogenetic tree. Jow2002.pdf
Papers on Microtubules –
Push-me-Pull-you Microtubules_TolicNorrelykke.pdf
– Dam1 kinetochore ring complex Microtubules_Westermann.pdf – Phase
diagram Microtubules_Fygensen.pdf
Actin – Evidence for the cap Actin_Carlier1984.pdf
Papers on Protein Folding -
ProteinFolding_Dill.pdf - ProteinFolding_Sali.pdf - ProteinFolding_Beck.pdf