BIOL 263 Molecular Biology and Genomics

Syllabus

Fall Semester 2016

November 23, 2016
(Latest update overrides all previous versions, electronic and print.)

MWF 10:10 AM-11:00 AM (Period 3)
Higley Auditorium

Dr. Wade Powell
FSH 202, PBX 5396
powellw[a]kenyon.edu
Office hours: M-1:30 - 3:30; T-9:30-11 and 3-4; F-11-noon
(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.
Recommended prerequisite or co-requisite: CHEM 231 and 232 (Organic Chemistry).

Reading Materials and Resources:

Required text: Watson et al., (2014) Molecular Biology of the Gene, 7th edition.
Journal Articles: Provided on moodle and/or in class. We will read one almost every week.
Web resources will be used in class and for your assignments. Look for the growing collection of these in moodle. Some links may also be found on this page.
Laptop Computers. Each student will semi-frequently need a laptop computer in class, either his/her own or one loaned by the Biology Department. Tablet devices and phones may be adequate, but they are rarely as effective as a computer. Please pay attention to the syallabus and my announcements about this.

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

Policies and Expectations:

Class attendance. 100% attendance is expected, and absences will detract from one's grade.
- Please see me immediately about conflicts due to sports events, performances, religious holidays, etc. In accordance with College policy (see Provost's web site), all students with scheduled conflicts must meet with me to initiate resolution by Friday, Sept.2.
- Please let me know in advance if you must miss class due to illness.
Participation. To participate fully in class, you must thoughtfully read the assigned material before each meeting. Expect to be called on; better yet, sing out or raise your hand! Please feel free to ask questions, add insights, correct the instructor's innacuracies, etc. at any time during class. Pull your weight in small group activities. At least once each exam cycle, you will submit a written self-assessment about the extent and nature of your participation. See Moodle for details.

Electronic devices. Full participation in class activities is crucial for success. Electronic devices can enhance particiatipation, but they can also become a distraction. Messaging, phone calls, social media, and unrelated web surfing are are distracting and disrespectful to your classmates and to me. Note taking, calculations, and accessing relevant databases are encouraged on your laptop, tablet, or phone.

Scheduling and Deadlines. Meeting deadlines is an important aspect of professionalism in science and all other careers. Please plan carefully. Exam schedules and deadlines for submitting assigned work are firm, and extensions will not be granted for conflcits with the workload for other courses. Accomodations due to illness or other personal situations are granted only in rare situations.

Academic Honesty. Conduct your work with integrity. Do not lie, cheat, or plagiarize. Do your own work on exams. In writing projects, properly acknowledge your sources of information, and acknowledge the help you receive from others. Kenyon's policy on academic honesty (Kenyon College Course Catalog) will be strictly observed. Explicit guidelines relating to final projects or other collaborative assignments will be discussed in class.

Special Needs. For assistance related to a physical, psychological or learning disability that may impact your ability to participate fully in the course, please speak with me and with Erin Salva, Director of Student Accessibility and Support Services (1-740-427-5453; salvae@kenyon.edu). All information and documentation of disability is confidential. Please see the Student Accessibility and Support Services web site for more information. Accommodation requests should be made immediately, well in advance of the first assigments and exams.

Title IX/VAWA. Kenyon College seeks to provide an environment that is free of gender bias, discrimination, and harassment. If you have been the victim of sexual harassment/misconduct/assault, interpersonal violence, or stalking, we encourage you to report this. If you report this to a faculty member, s/he must notify Kenyon's Title IX coordinator of any informaiton about the incident that you provide. Kenyon College's Title IX ane VAWA policy is available at: http://www.kenyon.edu/titleix

Assignments and Grades: Your grade is based on performance in the following areas:

10% Course Participation. 100% attendance is expected. To participate fully in class, you must thoughtfully read and annotate the assigned material before each meeting. Active, vocal contribution to class discussion and small group activities is expected from all members of the class and will be an important determinant of class participation grade.
10% Quizzes and assignments. Approximately ten quizzes over the semester. Quizzes can be given in class (announced or unannounced) or as take-home assignments. Every student gets one quiz "free pass." No notification or permission is required. This compensates for conflicts due to illness, busy schedule, athletics, performances, or any other etc. I encourage you to use your "free pass." Make-up quizzes will not be possible. For students who take every quiz, the lowest score will count as the "free pass: in the calculation of the quiz average.
60% Three Exams (each 20%). There are three regular exams in class.
20% Molecular Tutorial Project. A JMol Molecular Tutorial Project substitutes for the final exam. Ordinarily, two partners share a project. Examples of past projects and instructions for creating new ones can be viewed at Biomolecules at Kenyon. A working model must be ready for presentation to the class on Dec. 7. The final version, with zero broken links, is due December 15 at 9:30 pm. Both partners share full responsibility for the completed project.

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

Web resources
Biomolecules at Kenyon
Find Molecules: PDB and NIH
Companion web site for Watson text (requires access code from textbook; see front matter).

Course Schedule

Day	Date	Topic; interesting links	Primary Reading Assignment	Notes	Supporting Reading
*Part I: Molecular Interactions*
F	Aug 26	Course Introduction. DNA intro; B-DNA; A-RNA
M	Aug 29	Weak bonds. Amino Acids; CAP; Ident	Watson Ch 3, pp. 55-63; Ch. 6, pp. 121-122 + Fig. 6-2.
W	Aug 31	Adv DNA; Z-DNA ; Triplex; Quad; base tautomers; supercoiling; Topoisomerase	Watson Ch 4.
F	Sept 2	AA2 in proteins.	Ch 6, pp. 121-129.		Ch. 6, pp. 130-144.
M	Sept 5	Methods for Solving Protein Structures. Intro to pdb and JMOL	Protein Purification: Ch. 7, pp. 148-149. Ch 4, p. 88. NIH Structure Primer basic X-ray; Fourier transform; FT applet; another explanation (pdf). Cryoelectronmicroscopy ("Cryo-EM"); Cryo-EM Primer. Solution NMR		How do you tell if a reported structure is correct? Biochemistry vs. structural biology
W	Sept 7	Structure of a DNA binding protein, ADAR1 ADAR1 structures in rcsbPDB	Schwartz 99; pdb; The famous Gillen guide to reading journal articles.		Vocab; Human ADAR1; ADAR activity and consequence
*Part II: Gene Expression*
F	Sept 9	Transcription initiation, termination Structures: RNAP open complex; RnaPol-Euk; movies!	Watson Ch 13, pp. 429-442 and pp. 445-447.
M	Sept 12	Transcription Elongation; transcriptional road blocks	Epshtein & Nudler 2003 [Background: Conaway et al. 2003 (2nd and 3rd paragraphs); Watson Ch. 13, pp. 442-445		Electrophoresis: Watson Ch 7, pp. 148-149. DNA footprinting: Watson Ch. 7, pp. 184-185.
W	Sept 14	Bacterial Gene Regulation at level of transcription initiation.	Watson Ch 18, pp. 615-636		CAP-CTD; Lac repressor; Benoff Cooperative binding
R	Sept 15	Seminar: Gunnar Kwakye, Oberlin College 4:00 PM in (Higley Auditorium)	Disease x Toxicant Interaction in Parkinson's Disease: Role of alpha synuclein in cadmium neurotoxicity
F	Sept 16	Regulation of intiation, cont'd; Regulation of events after initiation: Attenuation in E. coli.	Watson Ch. 20, pp. 707-708;
M	Sept 19	Unique mechanism of attenuation in Bacillus. TRAP-RNA;	Antson 99;
W	Sept 21	Riboswitches	Watson Ch. 20, pp. 701-708; Soukup 2004 review riboswitch methods/data		Breaker Lab Riboswitch site (Yale) &movie
F	Sept 23	Exam I (in class) Points to ponder for the exam (updated 9/17/16).			score distribution
M	Sept 26	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 28	Eukaryotic Transcriptional Regulation; Spec. TFs. Identify	Watson Ch, 19, pp. 657-665 + 669-686
R	Sept 29	Seminar: Jon Lorsch, Director of National Institute of General Medical Sciences	4:15 PM, HIG AUD
F	Sept 30	Eukaryotic Transcription, cont'd.
M	Oct 3	Eukaryotic Transcription Research: Promoter Clearance	Pal et al. 2005
W	Oct 5	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 7	October Reading Days; No Class
M	Oct 10	Research in Eukaryotic Transcriptional Regulation: Chromatin Immunoprecipitation; Histone acetyltransferase recruitment Due date: Molecular Tutorial Proposal	Sharma 2002		ChIP:Watson Ch. 21, pp. 751-752; 778-780. Chromatin IP; cross-link chemistry PCR: Watson Ch. 21, pp. 751-752 Remember PCR?
W	Oct 12	Transcript Splicing; Splicing2; Spliceosome	Watson Ch. 14: pp. 467-477, 480-487, 491-496.
R	Oct 13	Seminar: Eric Alani, Cornell University	Double-strand break repair and crossing over during meiosis
F	Oct 14	Splicing, cont'd; Peptide bond formation; ribosome size			Family Weekend
M	Oct 17	Translation basics; initiation. Initiation. PDB; ribosome structural primer	Watson Ch. 15, pp. 509-535.
W	Oct 19	Translation elongation, termination.	Watson Ch. 15. pp. 535-549.
R	Oct 20	Natural Sciences Division Colloquium: Kerry Rouhier (Kenyon Chemistry Dept.) The Path to beta-alanine	Common Hour, TOM 101
F	Oct 21	Translation Research: ribosome hybrid state	Dorner et al. 2006		Watson Ch. 15: pp. 552-553
M	Oct 24	RNA Interference Animation from Nature Reviews Genetics .	Meister 04 (RNAi review paper) Watson Ch. 20, pp. 710-727.
W	Oct 26	miRNA paper
F	Oct 28	Exam II (points to ponder)
M	Oct 31	DNA Replication; Beta ring; DNA Rep; Replisome	Watson Ch. 9, pp. 257-287
T	Nov 1	Web Project Workshop, 7-10 PM
*Part III: DNA Replication, Repair, Recombination*
W	Nov 2	DNA Rep., cont'd.; Web Project Workshop, 7-10 PM	Watson Ch. 9, pp. 288-296
R	Nov 3	Web Project Workshop, 7-10 PM
F	Nov 4	Telomerase and telomeres. Telomerase structure. Telomeres 12-mer; 22-mer; Ten1, Stn1	Watson Ch. 9 p. 302-310. Blackburn 2000 review
Sun	Nov 6	Web Project Workshop, 4-6 PM
M	Nov 7	Telomerase Paper	Li et al. 2004
T	Nov 8	Web Project Workshop, 7-10 PM
W	Nov 9	Mutation and repair. Web Project Workshop, 7-10 PM	Watson Ch. 10
R	Nov 10	Web Project Workshop, 7-10 PM
F	Nov 11	Mutation/Repair paper	Obmolova 00
M	Nov 14	Homologous Recombination;	Watson Ch. 11: pp. 341-368 and 371-375		Experiments; RuvA; PNAS; Tn;
W	Nov 16	Class Cancelled			(Genome Editing: CRISPR and TALEN)
F	Nov 18	Knockout mice in molecular biology Knockout mice, cont'd	H19 Gene; Generation of Transgenic animals; MIT core facility
Nov. 19 - Nov 27: Thanksgiving Break
*Part IV: Special Topics -- Genomic-scale Applications*
M	Nov 28	DNA Sequencing; RNAseq:	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
W	Nov 30	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
F	Dec 2	Exam III
M	Dec 5	In-class pdb time
W	Dec 17	Student Project Presentations	.		Completed JMol Tutorial
F	Dec 9	Student Project Presentations	.
R	Dec 15	Revised Molecular Tutorials Due (corresponds with end of scheduled exam period)	No Broken Links		9:30 PM

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