Education and Infrastructure in Biological Physics

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Education and Infrastructure in Biological
Physics

• Raymond E. Goldstein
• Department of Physics
• Program in Applied Mathematics
• University of Arizona

With help from P. Nelson (UPenn) J. Kondev
(Brandeis)
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Education Infrastructure

• Educational initiatives are sprouting up at
  numerous universities
• and new textbooks are hitting the market.
  There are a few
• IGERT programs that address biological
  physics
• much remains to do we are on the cusp
• Key issues
• Convincing departments of the legitimacy of
  biological physics
• Setting up a serious dialog with biology
  departments (so they listen to the National
  Academy report (see below))
• Change the MCAT?!
• (iv) Assisting departments (physics, biology,
  mathematics) in the
• development of courses, majors (?),
  curricula
• (v) Laboratory courses
• (vi) Research infrastructure
• (vii) Support for graduate students
• (viii) Support for postdocs (from biology, from
  physics)
• (ix) Workshops
• (x) Centers (analogous to KITP, IMA, etc.)
• (xi) Role of applied mathematics (esp. more
  macro issues)

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BIO2010 report

http//books.nap.edu/
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BIO2010 report


http//books.nap.edu/
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BIO2010 report

http//books.nap.edu/
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Top seven reasons not to teach Biological Physics
Id love to, but...

• We cant justify a new elective course for our
  few majors

• We dont have enough manpower.

• Its already offered in chemistry or our medical
  school.

• My colleagues say, thats not really physics.

• Our students cant handle it.

• Im nervous!

• What would I cover, anyway? There are no books!

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Upper-level course material
Not just Physics students -- Not just Biology
students -- Also Engineering and Chemistry
students want and need this material, in courses
directed to their own background. Biological
physics and nanotechnology share a common
intellectual base.

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Mathematical models of bio-cartoons Two
realizations
BOOK
COURSES
Physical Biology of the Cell R. Phillips and J.
Kondev

• Physics of biological structure
• and function (RP, Caltech)
• Mechanical forces in molecular
• biology (JK, Brandeis)
• Seminar in biological physics (R.
• Meyer and JK, Brandeis)

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Biological physics major at Brandeis
Audience Students who like math and physics but
excited about research in the life-sciences.
Participating faculty Physics, Chemistry,
Biochemistry, Biology, and Neuroscience.
CORE
ELECTIVES

• Seminar in biophysics
• Intro physics labs
• Intro chemistry labs
• Intro biology labs
• Calculus
• Modern physics
• Thermal physics
• Quantum mechanics

• Physics of macromolecules
• Molecular motors
• Enzyme mechanisms
• Bioinformatics
• Computational neuroscience
• Structural molecular biology
• Biological physics, etc.

Curriculum
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BIPH11 Seminar in Biological Physics
Goals

• Build/maintain excitement about biological
  physics in spite of the
• introductory courses in Physics, Chemistry and
  Biology
• Develop physical intuition about biology via
  model calculations and
• estimates.
• Expose students to current research

Organization of the course follows the
introductory physics sequence.
Fall
Spring
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Arizona IGERT Lab Organization and Overview

• A core component of the NSF IGERT program at the
  University of Arizona
• Multidisciplinary Training at the Interface of
  Biology, Mathematics and Physics
• Awarded in 1998 as one of the first 15 IGERT
  programs in the U.S. to date the only
• one focused on this interface.
• Total funding 1.9 million over 5 years,
  supporting in steady state 15 students,
• includes 200K in equipment funding and 20K
  in yearly expenses for lab,
• biomathematics seminar, occasional workshops,

Faculty and Associates
Michael Tabor (Head)1,5 Raymond E.
Goldstein1,5 Neil H. Mendelson1,3 Timothy
Secomb1,6 Leslie Tolbert1,4 Koen
Visscher1,2,5 Lynn Oland4 Robert Reinking1,4
1Applied Mathematics 2Biochemistry Molecular
Biophysics 3Molecular and Cellular
Biology 4Neuroscience 5Physics 6Physiology
IGERTIntegrative Graduate Education and
Research Training
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A Wide Spectrum of Students
Fall 1999 (building the lab) Jose Maria
Celaya Contreras, Physics Dmitry Kondrashov,
Applied Math Fall 2000 Beth Bateman,
Physics Arne Eckstrom, Neuroscience
Margaret Evans, EEB Michael Kuecken, Applied
Math Tyler McMillen, Applied Math William
Nicol, Physics Tessa Osborne-Smith, Applied
Math Heather Seifert, BME Margaret
Turnbull, Astronomy (!) (BMEBiomedical
Engineering, EEBEcology Evolutionary Biology)
Fall 2001 Sunita Chatkaew, Physics Chris
Dombrowski, Physics Robert Ivens, BME
Patrick Marcus, BME Brooke McGuire, BME Fall
2002 Robert Lakatos, Applied Math Sergei
Pond, Applied Math Marcel Lauterbach, Physics
Silvia Lope-Piedrafita, Physics Sarah Swaim,
BME Hermann Uys, Physics
Summary a broad range of students, good
representation from women and minorities,
continual challenges meeting such a diversity of
backgrounds (!)
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Philosophy and Organization of the Lab Course

• A comprehensive treatment of methods is neither
  feasible nor desired.
• This is not a survey course on
  laboratory techniques!
• Our goal is that students understand, through
  lectures and experimentation,
• how mathematics, physics, and biology meet.
  The biology student
• will see perhaps unfamiliar mathematics and
  familiar biology.
• The math student will see what a PDE actually
  describes. They will
• both teach each other.

• Initial idea students rotate among 3-4
  experiments during the course of
• one semester, learning a variety of
  experimental techniques and ideas
• DOES NOT WORK!

Experimental research (MW 1-5 p.m.) weekly
discussion sections (F 1-2) to discuss
experimental problems or background (e.g. anatomy
of the brain, data acquisition, )
Theoretical background Warm-up experiment Microsco
py, Optical Trapping
Student Presentations
Laser Safety
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Infrastructure (and cost!)
RO water
Computers and work space
Discussion Presentations
Neuro
Trapping
Chemotaxis
Patterns
Wet chemistry
Dissections and sample preparation
Video Monitor
Capital equipment Renovations Yearly
Operating Budget 200K
150K 20K
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The IGERT Laboratory
wet chemistry
macro
chemotaxis
trapping
dissections
neuro
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Theoretical Background Material

• Overall emphasis scaling dimensional analysis

• Biological fluid dynamics and related subjects
  (Berg Purcell)
• scaling Navier-Stokes Reynolds number,
  Stokes drag
• diffusion and mixing
• Brownian motion (Einstein)
• Stokes-Einstein relation, equipartition
• Electrophysiology (Hodgkin Huxley)
• neuronal physiology, ion channels, pumps,
  action potentials
• Nonlinear Dynamics and Pattern Formation
  (Turing)
• diffusion and nonlinearity, fronts,
  reaction-diffusion eqns.,
• separation of time scales, spiral waves,
  Dictyostelium
• Microscopy Micromanipulation
• optics, methods (BF, phase, DIC),
  diffraction limits,
• optical traps, spectral analysis, filtering
• General techniques

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The Experiments (a Spectrum of Lengths)
Molecular Motors and Brownian Motion
optical trapping, kinesin stepping, fluctuating
barriers
10-9 m
Electrophysiology neurons, action
potentials, excitable media
10-6 m
Cell Motility and Chemotaxis world of low
Reynolds numbers, random walks, enhanced
diffusion
10-4 m
Pattern Formation bioconvection, waves,
instabilities
10-2 m
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Single Molecule Kinesin Bead Assay
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Optical Trapping Setup
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Microspheres Microtubules
DIC image of 1 micron silica beads and
microtubules
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Escape Over an Energy Barrier
DIC image of bead hopping between two minima of
a double-well potential created by two nearby
optical traps
Time series of particle position
Potential Energy Surface
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Life Cycle of Manduca Sexta
pupa
adult
eggs
1st larva
2nd larva
3rd larva
5th larva
4th larva
(30-50 days)
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Close-Up of Ganglion
Ganglion of interest primarily Responsible for
muscle control, dissected by students
Image from confocal microscope (neuroscience lab)
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Neuro Setup
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Spiking Neurons
Response to a short stimulus above threshold
for firing
60 mV
Response to a long stimulus intrinsic dynamics
of neurons and (likely) response from others.
2 sec
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A Bacterial Bath
fluorescent microspheres
parallel parking please
contact line
Examine effective diffusion constant of spheres
as a function of bacterial concentration
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Bacterial Bioconvection
Aerobic bacteria deplete dissolved oxygen, swim
up to air-water interface, create an unstable
density stratification, and persistent convective
rolls.
Bioconvective rolls in a thin (3 mm) suspension
in a petri dish
Bioconvective rolls in a 1 cm diameter Drop on a
solid surface (dark field)
(Sunita Chatkaew)
(J.O. Kessler)
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Example of a Research Spinoff
In one of the Friday discussion sessions Tyler
McMillan (Applied Mathematics) presented his
Ph.D. research on tendril perversions in
climbing vines. While theory (with Alain Goriely
and Michael Tabor) was quite well-developed, The
experimental situation was far less clear. This
eventually led to two of us (A.G. and R.E.G.) to
undertake a systematic experimental study of the
growth dynamics of tendril perversions, and to
develop a realistic theory for their formation.
3 cm
Goldstein and Goriely (2004)
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Challenges, Lessons Learned, and the Future

• Institutional
• view this as a College of
  Science effort, rather than
• associated with one or two
  departments
• (space, renovation , )
• Departmental
• flexibility in teaching
  obligations, very low
• student-faculty ratio (31)
  lab is also used
• for undergraduate lecture
  course in biophysics
• Funding Agencies
• NSF gets it (!), but the
  reporting burdens are large
• Faculty
• Specialized experiments mean
  only a few faculty
• can teach the course
• enormous time commitment 10
  hours/week in the lab!

• Future
• explore flexible uses for the
  lab rotations, as in biology,
• more fully integrated with
  research
• more distributed among
  departments