Integrated Quantitative Science 2. Signaling
Meeting times: Lecture (MWF 10:20, TTh 9:45), Lab (Th 1:30-4:30; physics and bio
space), Precept (T 1:30-2:30; physics space)
Text: Custom publish (math, physics, chemistry, biology: Cengage) and CS text
Time: 9 hours/week in class/lab/precept; 1.5 hours outside of class for each meeting
(class/precept/lab)
Evaluation (note: this is a rough estimate of what both semesters have agreed upon): 1000
total points:
i.
Lab: 250 points (x points on big presentations, rest broken down into y
points/week)
ii.
Exams: 5; 1st 4 are 100 points, the final is 125; exams can be part in
class/part take home- schedule 4 x 75 minute slots
iii.
Other activities (not lab): 225 points (15 pts/wk for 15 weeks); activities
can be take home or in class- instructor dependent (homework, quizzes,
etc)
Lecture Schedule
(OL: Ovidiu Lipan, KS: Krista Stenger, MK: Mike Kerckhove, DS: Doug Szajda, LG:
Lisa Gentile)
Date
Topic
Jan 11
Bridge to IQS-1, big picture-signaling. Intro to signaling, examples of
communications, set vocabulary. Set discussion in the context of: way to
generate a signal, receive a signal, propagate a signal, signal/noise ratio.
Lectures 1-2 (all): examples of signaling from each discipline (including,
but not limited to, immunology from bio).
Lectures 3-5 (KS): include description of where in pathways all
disciplines are going to be important).
Jan 18
Lectures 1-2 (KS): Strategies pathways use (paper: 3 habits of highly
effective signal transduction pathways as well as paper on discovery of
G-proteins and how they are part of pathways), idea of modularity of
proteins, genes, pathways (7-8 “fundamental pathways?), intro to types
of receptors; include experimental evidence
Lecture 3 (KS or LG): Intro to enzymes- regulatory strategies: (covalent
catalysis, GA/GB catalysis, zymogens, isozymes, metal ion catalysis)
Lecture period 4: Exam-1 (full or partial exam?)
Lecture 5 (MK): Basic calculus-type 1 integration: intro and practice:
Jan 25
Lectures 1-3 (MK): Basic calculus-type 1 integration: intro and practice,
con’t.
Lecture 4 (MK): Equilibrium/math for reactions that push towards
completion
Lecture period 5 (MK): Integration jeopardy (problem-solving session)
Feb 1
Lectures 1-3 (LG): Catalytic strategies (kinetics-differential versions):
rate laws (0, 1, 2 order), activation energy (temp dependence, Arrhenius),
reaction mechanisms, con’t.
Lecture 4 (and part of 5): (KS or LG): Michaelis-Menten
Lecture 5 (2nd part of): (MK): equilibrium
Feb 8
Lectures 1-5 (LG): equilibrium constants, relationship between kinetics
and equilibrium, factors affecting equilibrium (conc, vol, P, T,
LeChatelier, catalyst), acids and bases (Ka, Kb: types of acids and bases:
Bronsted, Lewis, Arrhenius, strong vs weak, mono/diprotic, pKas/aa side
chains), buffers, titrations
Feb 15
Lecture 1 (DS)
Lecture period 2: Exam-2
Lectures 3-5 (MK, OL): Brownian motion
Feb 22
Lectures 1-2 (MK): line integrals (tied into thermodynamics)
Lectures 3-5 (LG): thermodynamics: enthalpy, first law, work, heat,
calorimetry, heat capacity, enthalpies of reaction and formation second
law, entropy, spontaneity, free energy
March 1
Lectures 1-2 (LG): thermodynamics, con’t: enthalpy, first law, work,
heat, calorimetry, heat capacity, enthalpies of reaction and formation
second law, entropy, spontaneity, free energy
Lecture period 3 (LG, MK, OL): Problem solving session
Lecture 4 (LG and MK): example from protein folding of polynomial
approximation. (The heat capacity function is an example of thisquadratic approximations only)
March 8
Lecture 5 (DS): Shannon’s law and entropy
Lecture 1 (DS): Shannon’s law and entropy, con’t
Lecture period 2: Exam 3
Lectures 3-5: Rotational kinematics: (OL, MK)
March 15
Spring break
March 22
Lecture period 1: problem solving session
March 29
Lectures 2-5: Rotational kinematics, con’t: (OL, MK)
Lectures 1-3: Rotational kinematics, con’t: (OL, MK)
Lecture period 4: Exam 4
Lecture 5 (KS): CXCR4 signaling pathway: chemokine- GPCR, HIV
April 5
Lecture 1 (OL):10 minute movie and discussion of what’s happening in
the pathway (just portion of pathway: receptor-effector interaction),
lines/arrows
Lecture 2 (OL, MK): writing equations for the pathway
Lecture period 3: Problem solving section
Lectures 4-5 (OL, DS): simulations, introduction of a delay (need for
numerics), going back to measurements (need to find this in literature)
April 12
Lecture 1 (OL, KS, MK): Transport/trafficking
Lecture period 2: Exam 5
Lecture 3 (OL, KS, MK): Transport/trafficking, con’t
Lectures 4-5 (DS): Anti-viral software and resistance to them, lack
diversity that biol. systems have- what happens without them? Viruses
that mutate in wild on purpose.
April 19
Keep free for spill-over
Precept Schedule
Date
Jan 12
Jan 19
Jan 26
Feb 2
Feb 9
Feb 16
Feb 23
Topic
Intro to pathway for lab-1, intro to the first lab module (KS)
Plate cells for week-2 lab (KS, LG) plus demonstration of poor/good oral
presentation (DS)
Intro to electrophoresis/Western blots and background for the NO assay
(KS)
Real time q-PCR theory (AH), math and curve fitting (MK)
Intro to neural networks (DS)
Con’t of neural network discussion (DS)
Math background for the Brownian motion lab (MK)
March 2
March 9
How Brownian motion ties in with transport and trafficking in biology,
osmosis (OL)
Inheritance-1 (DS)
March 16
March 23
March 30
April 6
April 13
April 20
Spring break
Intro to AIDS and HIV protease (LG)
Background into types of inhibitors and KI determination (LG)
Intro to ITC (LG)
Inheritance-2 (DS)
Intro to signal propagation/waves (OL)
Laboratory Schedule
Date
Jan 14
Jan 21
Jan 28
Feb 4
Feb 11
Feb 18
Feb 25
March 4
March 11
March 18
March 25
April 1
April 8
April 15
April 22
Topic
(KS) Cell culture technique, start cultures, immunofluorescence
(KS) Activate cells early, harvest supernatants and lysates, protein assays
(KS) Run gels, set up Western blots (iNOS), real time q-PCR
(KS) Western blots (iNOS), real time q-PCR
(DS) Neural networks-1: development
(DS) Neural networks-2: training plus analysis
(OL, MK, DS) Brownian motion-1: movement of fluorescence beads in
cells, collect image in microscopy lab and analyze
(OL, DS, MK) Brownian motion-2: simulation
Student oral presentations (all groups)
Spring break
(LG) HIV-1 protease-I: kinetics of substrate binding to both wt and
MDR-HM (multidrug resistant-hexa mutant) protease:
measurement of initial velocity, investigation of how initial velocity
depends on [E], Km determination, Vmax determination. How have
kinetics been affected in the MDR protease?
(LG) HIV-1 protease-II: kinetics of inhibition by two anti-HIV drugs to
both wt and MDR-HM protease: determination of KI values. How has
inhibition been affected in the MDR protease?
(LG) HIV-1 protease-III: thermodynamics. ITC of both wt and MDRHM protease binding to two antid
binding been affected in the MDR protease?
(LG/CP) HIV-1 protease-IV: molecular modeling (computation).
Visualization of crystal structure (apo and drug bound), location of
mutants in MDR-HM, location of drug binding pockets, prediction of
how mutants confer resistant to these drugs.
(OL) Signal propagation/waves: NS application (frog hearts?)
Preliminary thoughts on IQS-2 lab assessment:
1. Oral scientific communication: early on, a precept period will be used to
demonstrate aspects of both good and poor oral communication. Throughout the
semester, students will give one oral presentation communicating the results of
one lab module (HIV-protease not included). Done before spring break- first half
of lab.
2. Written scientific communication: a formal written report will be done for the 4
week HIV protease module. In preparation for this, assessment for other lab
modules will focus on various aspects of a formal written report (ie how to create
figures, present data, write conclusions, etc). Done after spring break- 2nd half of
lab.