BIOL 263: Molecular Biology


Syllabus

Fall Semester 2017

August 15, 2017
(Latest update overrides all previous versions, electronic and print.)

MWF 10:10 AM-11:00 AM (Period 3)
SMA 215

Dr. Wade Powell
FSH 202, (740) 427-5396
powellw[a]kenyon.edu
Office hours:

M,T,R,F: 1:30 - 3:00 PM
(and by appointment; sorry, never on Wednesdays)


Introduction:
The molecular and genomic basis of life is at the heart of modern biology. In BIOL 263, we will learn techniques and explore research questions at the forefront of molecular biology, focusing on the mechanisms by which the information of the genome is expressed to form the functional molecules of living cells and organisms. The processes of DNA replication, recombination and repair, transcription of RNA from DNA templates, and translation of RNA into protein are discussed in the context of current research, frequently using primary literature. The function of genes and regulation and measurement of gene expression are treated in depth. Students analyze and publish interactive tutorials on the structure and function of key macromolecules. This intermediate-level course presumes a strong background in the basics of protein structure/function, central dogma processes, fundamental molecular techniques for manipulating nucleic acids and proteins, and general chemistry.
Required prerequisites: BIOL 115, 116; one year of chemistry (Intro or Honors Intro); or permission of the instructor.
Recommended prerequisite or co-requisite: CHEM 231 and 232 (Organic Chemistry).


Reading Materials and Resources:

All reading assignments must be completed before class on the date indicated on syllabus.


Policies and Expectations:

Assignments and Grades: Your letter grade is assigned at the end of the course based on performance in the following areas:


Important Links:
(Note: Some resources can only be accessed on Kenyon campus.)

Course Schedule

Day
Date
Topic; interesting links
Primary Reading Assignment
Supporting Reading
Part I: Molecular Interactions
F
Aug 26
5
Course Introduction. Nucleic acid and nucleotide structure.
  DNA intro; B-DNA; A-DNA
M
Aug 28
Amino acid structure.  Weak bonds in macromolecules.  Watson Ch 3, pp. 55-63; Ch. 6, pp. 121-122 + Fig. 6-2.  Weak bonds. Amino Acids; CAP; Ident
W
Aug 30
Advanced DNA structure:  Base Tautomers, Supercoiling Watson Ch 4. Adv DNA; Z-DNA ; Triplex; Quad; base tautomers; supercoiling; Topoisomerase
F
Sept 1
Protein Structure: Helices, strands, sheets, interactions between aa residues

Ch 6, pp. 121-129.

AA2 in proteins.
Ch. 6, pp. 130-144.
M
Sept 4

Methods for Solving Macromolecular Structures.

Intro to pdb and JMOL

RSCB Protein Data Bank

Protein Purification: Ch. 7, pp. 148-149. Ch 4, p. 88.

NIH Structure Primer

basic X-ray; another explanation (pdf).

Cryoelectronmicroscopy ("Cryo-EM"); Cryo-EM Primer.

Solution NMR

Protein purification by liquid chromatography

Critical Thinking:
How do you tell if a reported structure is correct?

Biochemistry vs. structural biology

W
Sept 6

Structure of a DNA binding protein, ADAR1


 

Schwartz 99;
pdb;

ADAR1 structures in rcsbPDB
ADAR activity and consequence


The famous Gillen guide to reading journal articles.
Vocab;


Part II: Gene Expression
F
Sept 8
Transcription initiation, elongation, termination
Watson Ch 13, pp. 429-447.  Structures: RNAP open complex; RnaPol-Euk; movies!
M
Sept 11
Transcription Research:  RNA polymerase "scrunching"

Kapanidis et al. 2006

Supporting Info

Watson Ch. 13, pp. 441-442

Background: Single-molecule techniques explained.

DNA footprinting: Watson Ch. 7, pp. 184-185.

W
Sept 13

Bacterial Gene Regulation at level of transcription initiation.

Watson Ch 18, pp. 615-636 CAP-CTD; Lac repressor; Benoff
Cooperative binding
R
Sept 14
Chemistry/BMB Seminar:
Susan Schroeder, Dept. of Chemistry and Biochemistry, University of Oklahoma
Exploring RNA structure, function, and energetics

F
Sept 15
Bacterial gene regulation, cont'd;
Regulation of events after initiation: Riboswitches, attenuation
Watson Ch. 20, pp. 703-708;
 -Soukup 2004 review
-Breaker Lab Riboswitch site (Yale) &movie
-riboswitch methods/data
M
Sept 18
Unique mechanism of attenuation in Bacillus.
Paper:  Antson 99

 
W
Sept 20
Catch-up

 


R
Sept 21
Biology/BMB Seminar:
Arianna Smith
Dept. of Obstetrics, Gynecology, and Reproductive Biology, Michigan State University and Biology Department, Kenyon College
Exploring the Role of Prenatal Maternal Stress on Allergic Asthma Development in Offspring
F
Sept 22
Exam I (in class).   score distribution
M
Sept 25
Eukaryotic Basal Transcription Factors. DAB Pol II; TBP; TAF; solving the structure of RNA pol II.
Watson Ch. 13 pp.448-464
gel shifts: Watson Ch. 7, pp. 183-184
chromatography: Ch. 7, pp. 173-177.
W
Sept 27
Eukaryotic Transcription, cont'd.
 
F
Sept 29
Eukaryotic Transcription Research:  GTFs and promoter clearance
 Pal et al. 2005  
M Oct 2
Eukaryotic Transcriptional Regulation Watson Ch, 19, pp. 657-665 + 669-686  
W
Oct 4
Nucleosomes & Transcriptional regulation; Histone Code. Nucleosome tutorial Watson Ch. 8 pp. 219-255; Ch. 19 pp. 665-669; Ch. 7, pp. 185-187.
Histone binding sites: Nature N&V 2006

 
F
Oct 6
October Reading Days; No Class  
M
Oct 9

Research in Eukaryotic Transcriptional Regulation: Chromatin Immunoprecipitation; Histone acetyltransferase recruitment


Sharma 2002

See moodle for guided meditation assignment.


ChIP:Watson Ch. 21, pp. 751-752; 778-780. cross-link chemistry

PCR: Watson Ch. 21, pp. 751-752 Remember PCR?

W
Oct 11
Due date: Molecular Tutorial Proposal
 (instructions and electronic submission page on moodle)
R
Oct 12
Biology/BMB Seminar:
Heidi Andersen, MD
Pediatric Infectious Disease, Cincinnati Children's Hospital
Metagneomic shotgun sequencing for detection of colonization, transmission, and invasion with multidrug resistant pathogens in high risk children
4:00 PM, HIG AUD
F
Oct 13

Transcript Splicing; Splicing2; Spliceosome

 Watson Ch. 14: pp. 467-477, 480-487, 491-496. Family Weekend;
Summer Science Posters
M
Oct 16
Splicing conclusion; Peptide bond formation; ribosome size Watson Ch. 15, pp. 509-535.  
W
Oct 18
Translation basics; initiation. Initiation. PDB; ribosome structural primer
 
F
Oct 20
Translation elongation, termination. Watson Ch. 15. pp. 535-549.
M
Oct 23
Translation Research: Ribosome hybrid state Dorner et al. 2006  Watson Ch. 15: pp. 552-553
T
Oct 24
Chemistry/BMB Seminar: 
Chris Neale, Center for Nonlinear Studies, Los Alamos National Laboratory
Structure/function of G-protein coupled-receptors

W
Oct 25
RNA Interference
Animation from Nature Reviews Genetics .
 Wilson and Doudna 2013 (RNAi review paper)
Watson Ch. 20, pp. 710-727.
 
F
Oct 27
Exam II (points to ponder)    
M
Oct 30
DNA Replication; Beta ring; DNA Rep; Replisome Watson Ch. 9, pp. 257-287  
Part III: DNA Replication, Repair, Recombination
W
Nov 1
DNA Replication, cont'd.;
Web Project Workshop, 7-10 PM
Watson Ch. 9, pp. 288-296  
R Nov 2 Biology/BMB Seminar:
Ann Miller, Dept. of Molecular, Cellular, and Developmental Biology, University of Michigan

Web Project Workshop, 7-10 PM
 Regulation and localization of RhoA GTPase in cytokinesis
 
F
Nov 3

Telomerase and telomeres. Telomerase structure. Telomeres 12-mer; 22-mer; Ten1, Stn1

Watson Ch. 9 p. 302-310.
Blackburn 2000 review
 
S Nov 5
Web Project Workshop, 4-6 PM    
M
Nov 6 

Replication Paper--Single-molecules replisome study: Are leading and lagging strad polymerases really coordinated?
Web Project Workshop, 7-10 PM

Graham et al. 2017

Guided meditation on moodle due at beginning of class
Don't ignore the supplemental information figures!
W
Nov 8

DNA Sequencing, RNAseq
Web Project Workshop, 7-10 PM

Watson Ch. 2, p. 40-41; Ch. 8, p. 199-208; Ch. 7, p. 158-171. cycle; pyrosequencing (454); illumina video; another illumina video; cheap genomes
R
Nov 9
Web Project Workshop, 7-10 PM    
F
Nov 10
Research:  ChiPseq
Estrogen Receptor Binding throughout the Genome
Hurtado, et al. 2011.

Supplementary info.

Integrates: Eukaryotic transcription factors, enhancer elements ChIP, NextGen sequencing, PCR, westerns, siRNAs, cell cycle, cancer
M
Nov 13

Mutation and repair

 

Watson Ch. 10

W
Nov 15
Homologous Recombination; Watson Ch. 11: pp. 341-368 and 371-375 Experiments; RuvA; PNAS; Tn;
F
Nov 17

Knockout mice in molecular biology Knockout mice, cont'd

 

H19 Gene; Generation of Transgenic animals; MIT core facility

 
Nov. 20 - Nov 24: Thanksgiving Break
M
Nov 27
CRISPR Genome Editing

W
Nov 29
Catch-up

F
Dec 1
Exam III    
M
Dec 4
In-class pdb time    
W
Dec 16
Student Project Presentations . Completed JMol Tutorial
F
Dec 8
Student Project Presentations

.

 
R
Dec 14
Revised Molecular Tutorials Due (corresponds with end of scheduled exam period) No Broken Links 9:30 PM
 
     

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