BIOL 263: Molecular Biology


Syllabus

Fall Semester 2019

UNDER CONSTRUCTION

Oct. 22, 2019
(Latest update overrides all previous versions, electronic and print.)

MWF 09:10 AM-10:00 AM (Period 2)
SMA 201

Dr. Wade Powell
Proper Nouns: "Wade," "Professor Powell," "Dr. Powell" all good
Pronouns: he/him/his
FSH 202/204, (740) 427-5396
powellw[a]kenyon.edu

Office hours:
M 3-4; T 2:30-3:30; W 10
-noon; R 10-11
(and by appointment)


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 (CHEM 121-124 or CHEM 122); or permission of the instructor.  Organic Chemistry is not required.

Learning Goals:


Reading Materials and Resources:



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
Primary Reading Assignment
Supporting Reading
Part I: Molecular Interactions
F

Aug 30 

 
Course Introduction. Nucleic acid and nucleotide structure.
  DNA intro; B-DNA; A-DNA
M
Sept 2
Amino acid structure.  Weak bonds in macromolecules.  Watson Ch 3, pp. 55-63; Ch. 6, pp. 121-122, especially Fig. 6-2.   Weak bonds. Amino Acids; CAP; Ident
W
Sept 4
Advanced DNA structure:  B/A/Z-DNA structures; Base Tautomers, Supercoiling Watson Ch 4. Adv DNA; Z-DNA ; Triplex; Quad; base tautomers; supercoiling; Topoisomerase
F
Sept 6
Protein Structure: Helices, strands, sheets, interactions between aa residues

Ch 6, pp. 121-129.

AA2 in proteins.
Ch. 6, pp. 130-144.
M
Sept 9

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.

A summary of structural biology approaches

NIH Structure Primer

Protein purification by liquid chromatography

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

Biochemistry vs. structural biology

W
Sept 11

Structure of a DNA binding protein, ADAR1


 

Schwartz 99;
ADAR1 structures in rcsbPDB
ADAR activity and consequence


The famous Gillen guide to reading journal articles.
Vocab;


Part II: Gene Expression
F
Sept 13
Transcription initiation, elongation, termination
Watson Ch 13, pp. 429-447.  Structures: RNAP open complex; RnaPol-Euk; movies!
M
Sept 16
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 18

Bacterial Transcription Regulation at level of transcription initiation.

Watson Ch 18, pp. 615-636 CAP-CTD; Benoff 1999;
Liu 2017
Lac repressor
Cooperative binding
F
Sept 20
Bacterial transcription 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 23
Unique mechanism of attenuation in Bacillus.
Paper:  Antson 99 trp RNA-binding attenuation protein.

 
W
Sept 25
Catch-up or review

 


F
Sept 27
Exam I (in class) .  
M
Sept 30
Eukaryotic General Transcription Factors. DAB Pol II; TBP; TAF; solving the structure of RNA pol II.
Watson Ch. 13 pp.448-464
Techniques:
gel shifts: Watson Ch. 7, pp. 183-184
chromatography: Ch. 7, pp. 173-177.
W
Oct 2
Eukaryotic Transcription, cont'd.
PIC assembly structures
PIC assembly movie
F
Oct 4
Eukaryotic Basal Transcription Research:


M
Oct 7
Eukaryotic Transcriptional Regulation:  Regulatory elements and transcription factors
Watson Ch, 19, pp. 657-665 + 669-686  
W
Oct 9
Nucleosomes & Transcriptional regulation;  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 11
October Reading Days; No Class  
M
Oct 14


CORRECTED SCHEDULE FOLLOWS FROM HERE

 

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

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

W
Oct 16
Research in Eukaryotic Transcriptional Regulation: Chromatin Immunoprecipitation; Histone acetyltransferase recruitment Sharma 2002

See moodle for guided meditation assignment.

F
Oct 18
Transcript Splicing; Splicing2; Spliceosome   Watson Ch. 14: pp. 467-477, 480-487, 491-496. Family Weekend;
Summer Science Posters!
M
Oct 21
Splicing conclusion
Translation: Peptide bond formation; ribosome size
Watson Ch. 15, pp. 509-515; 521-528   Revised Due date: Molecular Tutorial Proposal (instructions and electronic submission page on moodle)
W
Oct 23
Translation basics; initiation. Initiation. PDB; ribosome structural primer
Watson Ch. 15, pp. 528-535  
F
Oct 25
Translation elongation, termination. tRNA charging Watson Ch. 15. pp. 535-549; 515-520 Watson Ch. 15: pp. 552-553
M
Oct 28
Translation Research: Ribosome hybrid state Dorner et al. 2006

See moodle for guided meditaton

 
W
Oct 30
RNA Interference
Animation from Nature Reviews Genetics .
 Wilson and Doudna 2013 (RNAi review paper)
Watson Ch. 20, pp. 711-727.
 
F
Nov 1
Exam II (points to ponder)    
Part III: DNA Replication, Repair, Recombination
M Nov 4 DNA Replication; Beta ring ; DNA Rep; Replisome
Web Project Workshop, 7-10 PM; TOM 101
Watson Ch. 9, pp. 257-277
W
Nov 6
DNA Replication, cont'd.;
Web Project Workshop, 7-10 PM; TOM 101
Watson Ch. 9, pp. 277-288; 293-296
 
R Nov 7 Web Project Workshop, 7-10 PM; SMA 201

F Nov 8 Replication Paper--Single-molecule replisome study:
Are leading and lagging strand polymerases really coordinated?
Graham et al. 2017
Guided meditation on moodle due at beginning of class
Don't ignore the supplemental information figures!
Sun Nov 10
Web Project Workshop, 7-10 PM; SMA 201
   





M
Nov 11
DNA Mutation and Repair
Watson Ch. 10

W
Nov 13
DNA Repair Research


F
Nov 15
Homologous Recombination;
Watson Ch. 11: pp. 341-368 and 371-375 Experiments; RuvA; PNAS; Tn;
M
Nov 18
Telomerase and telomeres. Telomerase structure. Watson Ch. 9 p. 302-310.
Blackburn 2000 review

W
Nov 20
Paper:  Ter, tert, and cancer Li et al 2004
F
Nov 22

CRISPR Genome Editing

Ch. 20: 706; 709-711
 
M-F Nov 25-29
Thanksgiving Break; no class


M
Dec 2
Generation of knockout mice by homologous recombination


W
Dec 4
Paper:  Application of CRISPR to characterize lncRNA function Espinosa 2016 (News & Views piece)
Paralkar 2016 (research article)

F
Dec 6
Exam III    
M
Dec 9
In-class pdb time    
W
Dec 11
Student Project Presentations . Completed JMol Tutorial
F
Dec 13
Student Project Presentations

.

 
W
Dec 18
Revised Molecular Tutorials Due 9:30 PM (corresponds with end of scheduled exam period) Final Submission (via moodle)

 
     

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