BIOL 263: Molecular Biology


Syllabus

Fall Semester 2018

December 18, 2018
(Latest update overrides all previous versions, electronic and print.)

MWF 10:10 AM-11:00 AM (Period 3)
TOM 101

Dr. Wade Powell
FSH 202, (740) 427-5396
powellw[a]kenyon.edu
Office hours:
Tuesdays 12:30-2:30 PM (open) + 7:30-8:30 PM (by appointment)
Wednesdays 11:00 AM - 1:00 PM
Thursdays 9:30 AM - 10:30 AM
(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 (Intro or Honors Intro); or permission of the instructor.

Learning Goals:


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 30 

 
Course Introduction. Nucleic acid and nucleotide structure.
  DNA intro; B-DNA; A-DNA
M
Sept 3
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 5
Advanced DNA structure:  Base Tautomers, Supercoiling Watson Ch 4. Adv DNA; Z-DNA ; Triplex; Quad; base tautomers; supercoiling; Topoisomerase
R Sept 6 Biology/BMB Seminar: Harry Itagaki, Kenyon College

F
Sept 7
Protein Structure: Helices, strands, sheets, interactions between aa residues

Ch 6, pp. 121-129.

AA2 in proteins.
Ch. 6, pp. 130-144.
M
Sept 10

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 (newly added)

NIH Structure Primer

basic X-ray;
Amore complicated X-ray 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 12

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 14
Transcription initiation, elongation, termination
Watson Ch 13, pp. 429-447.  Structures: RNAP open complex; RnaPol-Euk; movies!
M
Sept 17
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 19

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 21
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 24
Unique mechanism of attenuation in Bacillus.
Paper:  Antson 99trp RNA-binding attenuation protein.

 
W
Sept 26
Catch-up

 


R
Sept 27
Biology/BMB Seminar: Priscilla Erickson '09
Biology Department, University of Virginia


F
Sept 28
Exam I (in class).   score distribution
M
Oct 1
Eukaryotic General 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
Oct 3
Eukaryotic Transcription, cont'd.
PIC assembly structures
PIC assembly movie
R Oct 4 Biology/BMB Seminar: Courtney Sulentic
Dept. of Pharmacology and Toxicology, Wright State University
A genetic polymorphism + chemical exposure = Autoimmunity??

F
Oct 5
Eukaryotic Transcription Research:  GTFs and promoter clearance
 Pal et al. 2005  Background Review:  Luse 2013
M
Oct 8
Eukaryotic Transcriptional Regulation Watson Ch, 19, pp. 657-665 + 669-686  
W
Oct 10
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 12
October Reading Days; No Class  
M
Oct 15

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 17
Transcript Splicing; Splicing2; Spliceosome Watson Ch. 14: pp. 467-477, 480-487, 491-496.  Due date: Molecular Tutorial Proposal (instructions and electronic submission page on moodle)
F
Oct 19
Splicing conclusion; Peptide bond formation; ribosome size  Watson Ch. 15, pp. 509-528. Family Weekend;
Summer Science Posters!
M
Oct 22
Translation basics; initiation. Initiation. PDB; ribosome structural primer Watson Ch. 15, pp. 528-535  
W
Oct 24
Translation elongation, termination. Watson Ch. 15. pp. 535-549.  
F
Oct 26
Translation Research: Ribosome hybrid state Dorner et al. 2006 Watson Ch. 15: pp. 552-553
M
Oct 29
RNA Interference
Animation from Nature Reviews Genetics .
Wilson and Doudna 2013 (RNAi review paper)
Watson Ch. 20, pp. 710-727.
 
W
Oct 31
Catch-up Day    
F
Nov 2
Exam II (points to ponder)    
Part III: DNA Replication, Repair, Recombination
M Nov 5 DNA Replication; Beta ring; DNA Rep; Replisome
Web Project Workshop, 7-10 PM; TOM 201
Watson Ch. 9, pp. 257-287
W
Nov 7
DNA Replication, cont'd.;
Web Project Workshop, 7-10 PM; TOM 101
Watson Ch. 9, pp. 288-296  
R Nov 8 Web Project Workshop, 7-10 PM; SMA 201

F Nov 9 Replication Paper--Single-molecules 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 11
Web Project Workshop, 7-10 PM; SMA 201
   
M
Nov 12 
Telomerase and telomeres. Telomerase structure. Telomeres 12-mer; 22-mer; Ten1, Stn1 Watson Ch. 9 p. 302-310.
Blackburn 2000 review

W
Nov 14
Paper:  Ter, tert, and cancer Li et al 2004

F
Nov 16
Homologous Recombination;
Watson Ch. 11: pp. 341-368 and 371-375 Experiments; RuvA; PNAS; Tn;
Nov 17-25
Thanksgiving Break

M
Nov 26

Knockout mice in molecular biology

H19 Gene; MIT core facility

W
Nov 28
Mutation and repair Watson Ch. 10
F
Nov 30

CRISPR Genome Editing


 
M
Dec 3
Paper:  Application of CRISPR to characterize lncRNA function Espinosa 2016 (News & Views piece)
Paralkar 2016 (research article)


W
Dec 5
Catch-up

F
Dec 7
Exam III    
M
Dec 10
In-class pdb time    
W
Dec 12
Student Project Presentations . Completed JMol Tutorial
F
Dec 14
Student Project Presentations

.

 
R
Dec 18
Revised Molecular Tutorials Due (corresponds with end of scheduled exam period) No Broken Links 9:30 PM
 
     

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