ECOL/MCB 320H: Honors Genetics

Latest asignment, due 3 December, 2001

Time: Mondays, 2:00 - 2:50 pm
Location: PAS 220, moving to Social Sciences 132 (starting 10 Sept)
Instructor: Linda Restifo, Associate Professor of Neurobiology
- Contact info: LLR@neurobio.arizona.edu; 621-9821 (office line with answering machine); office: 423 Gould-Simpson Bldg (clip messages to door)
- Office hours: Tuesday, 10-11 am, 408 Gould-Simpson Bldg, or by appointment

Overview

Students registered for ECOL/MCB 320H have an additional hour of class time (Mondays, 2:00 - 2:50 pm) beyond the four dedicated to lectures and discussion of problem sets. Attendance at the "fifth hour" is mandatory for 320H students.
The goals of the Honors segment are:
- to present a fascinating story of how genetic strategies are used to solve a biological puzzle--in this case, the mechanisms underlying circadian rhythms (intrinsic biological rhythms about one day in length);
- to enhance students' abilities to read and understand the scientific literature, including primary research articles;
- to improve students' analytical reasoning skills, especially those used for evaluating experimental design and data;
- to enhance students' understanding of articles in the lay press (magazines and newspapers) that deal with genetics; and
- to improve students' abilities to write about genetics concepts and approaches.

Format

Combination lecture and discussion
Class participation is strongly encouraged and will be a component of grading (see below)
Reading assignments will come mostly from the primary and secondary literature. In some cases, hard copies of the readings will be placed on Reserve at the Science & Engineering Library. Others will be available on the Web. Assignments must be read before class. Students often find it useful to bring a copy of the reading assignment with them to class. The first reading assignment will be discussed on Monday, August 27.
For many of the class sessions, there will be a brief writing assignment, usually based on the readings. The written assignments will be collected at the beginning of class. You should keep a copy of your writing to refer to during class discussion. Hand-written assignments are acceptable if and only if your handwriting is easy to read! If you have any doubts, please type.
Late assignments will not be accepted without prior approval. No make-up assignments will be given.

Assessment and grading

Honors students can earn up to 30 points, which will be added to their total score for the rest of the course. Exams and problem sets have a maximum total point score of 620. See Dr. Walsh for details.
The 30 points will be divided between written assignments (24 pts) and class participation (6 pts).

Assignments

Reading assignment for Monday, August 27, 2001
- Moore-Ede, Sulzman & Fuller (1982). "A physiological system measuring time." In The Clocks that Time Us, Physiology of the Circadian Timing System, pp 1-29, Cambridge: Harvard U. Press. (3 copies of this book chapter have been placed on Reserve in the Science & Engineering Library. They can be obtained at the Circulation Desk.)
- While reading, think about the following and be prepared to discuss in class:
  1. What does the phenomenology of circadian rhythms suggest about their molecular mechanism(s)?
  2. How could a genetic approach be used to reveal those mechanisms?
  3. Do you think the circadian rhythm mechanisms of different animal species are relatively similar or relatively different? What about plants vs. animals?
Reading assignment for Monday, September 10, 2001
- Read these two:
  1. Moore-Ede, Sulzman & Fuller (1982)Ê"Characteristics of circadian clocks"Chapter 2 inThe Clocks that Time Us, Physiology of the Circadian Timing System,Cambridge: Harvard U. Press, pp 30-40, 50-56, 60-64, 73-76, 82-87, 97, and 109.
  2. Konopka RJ and Benzer S (1971) Clock mutants of Drosophila melanogaster Proc. Natl. Acad. Sci. USA 68:2112-2116
  3. These readings have been deposited at the Main Library for scanning into theElectronic Reserve system, accessible through SABIO (Quick Links ---> Reserves) or at : http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3 They will be listed under ECOL 320H.*****The password for this course is "fruitfly" (password is case-sensitive)*****
- Write a 1-page mini-paper, answering the following questions regarding the Konopka and Benzer article:1. What are the most significant findings of the reported study?2. What are the most interesting questions raised by the findings?
Reading assignment for Monday, September 17, 2001
- Read and be prepared to discuss: Bargiello, Jackson and Young (1984) Restoration of circadian behavioral rhythms by gene transfer inDrosophila Nature 312: 752-754. This article is available through the Library's electronic reserve system: http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3
- There is no writing assignment, but think about the following two questions:
  1. What part of the circadian rhythm mechanism is most likely controlled by the period gene?
  2. How many additional genes/proteins are likely to be required to operate the clock mechanism in a fly? in a mammal?
Reading assignment for Monday, September 24, 2001
- re-read Bargiello et al. (1984), Nature312:752-754 The article is available through the Library's electronic reserve system: http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3. See also pp. 618-619 in the Griffiths' et al. textbook for a description of P-element-mediated germline transformation. We will discuss this in class on Monday.
  Then, write: Find 1-2 statements in the article that fall into each of these categories of interpretation: 1. "Conclusion": strongly supported by abundant data; all competing conclusions either ruled out or not supported by existing data. 2. "Working model": overall weight of evidence favors the interpretation, but additional experiments needed to rule out alternatives. 3. "New hypothesis": consistent with the available data, but too little information available to rule other interpretations in or out. (This category often appears in the setting of unexpected results.) 4. "Speculation": a plausible idea that could explain available data, but currently no data available that are directly relevant to the interpretation.
Reading assignment for Monday, October 1, 2001
- Hardin PE, Hall JC and Rosbash M (1990) Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343:536-540. Bring a copy of the paper to class.
- Based on this article and the others we have read to date,write a short (1-2 pages) paper answering the following:
  1. In your own words (ie, do not quote the paper), state the two most important interpretations presented by Hardin et al.
  2. For each one, describe in your own words the experimental data that support the authors' interpretations.
Reading assignment for Monday, October 8, 2001
- HCurtin KD, Huang ZJ and Rosbash M (1995) Temporally regulated nuclear entry of the Drosophila periodprotein contributes to the circadian clock. Neuron 14:365-372.
- There is no writing assignment for Oct. 8.

Reading assignment for Monday, October 15, 2001

Find a statement of experimental observation(s) and quote it directly from the paper, making note of what page it's from.
Explain, in your own words, the interpretation(s)that your selection experimental observation(s) are being used to support.
Explain the key features of the new hypothesis proposed in the Discussion (Fig. 4).
Describe briefly one experiment that could be done to test this new hypothesis. Don't worry too much about technical details or feasibility, but don't propose something that is obviously impossible to do.

Please note: The previous writing assignments were graded in a roughly all-or-none fashion (e.g., if you turned it in on time, you got full credit). Starting with this assignment, papers will be graded on a 3-point scale. [ALSO: there is a new reading--Sehgal et al., 1994--available through the library's electronic reserves, but I've decided to postpone that until the following week.]

Reading assignment for Monday, October 22, 2001

Sehgal et al. (1994).Ê Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science 263:1603-1606.This article is available through the Library's electronic reserve system: http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3
There is no writing assignment for Oct. 22.

Reading assignment for Monday, October 29, 2001

Zeng et al. (1996). A light-entrainment mechanism for the Drosophila circadian clock. Nature 380:129-135..This article is available through the Library's electronic reserve system: http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3. Please also read "The Demise of Bill," which was handed out in class on Oct. 22nd.
Writing assignment: This paper presents data derived from many different experimental techniques. First, choosethree different techniques used in this paper. Then, for each one, state:
1. an experimental observation made using that method (quote directly from the paper and note what page of the article it is from--not the page number of the eReserve file).
2. in your own words, the authors' interpretation of that experimental observation

Reading assignment for Monday, November 5, 2001

Re-read Zeng et al. (1996). A light-entrainment mechanism for the Drosophila circadian clock. Nature 380:129-135..This article is available through the Library's electronic reserve system: http://ereserves.library.arizona.edu/ers_search/OSCRsrchform.php3.
Writing assignment:
1. In your own words, explain the new hypothesis that is proposed at the end of Zeng et al., including the proposed molecular mechanism of circadian clock entrainment by light.
2. Choose one feature of the model and propose an experiment that could test its validity. Describe the experiment in as much detail as you can. Make sure to specify what results you would expect if that feature of the model is correct vs. if it is not correct.

No Class, Monday, November 12, 2001

Reading assignment for Monday, November 19, 2001

The following pair of papers were published back-to-back in the July 10, 1998 issue of Cell. Please READ bothabstracts and select one of the papers to read in detail. Use that paper as the basis for your answer to the question below.
1. Price et al. (1998). double-time is a novel Drosophila clock gene that regulates PERIOD protein accumulation. Cell 94:83-95.
2. Kloss et al. (1998). The Drosophila clock genedouble-time encodes a protein closely related to human casein kinase Ie. Cell 94:97-107. PLEASE NOTE: both papers contain color figures and the cover photo of that issue ofCell is also related to these articles.
These papers are available on the web through university library subscriptions:
- Medical School: www.ahsl.arizona.edu/journals/ejrnls
- Engineering Library: dizzy.library.arizona.edu/ej/ej.shtml#subscriptions You can access these electronic subscriptions from any U of A computer or, if you use dakota.com as your internet provider, from home.
- Writing assignment: First, indicate which of the two papers you selected (Price et al., 1998, or Kloss et al., 1998). Then, answer the following:
  1. What, in your opinioin, are the two most significant findings in this paper?
  2. For each finding, how was a specific experimental method used to reveal it?
  3. For each finding, what are its implications for the mechanistic model of circadian clock function?
Latest assignment: Monday, December 3, 2001
Monday, December 3, 2001
READ:
Allada et al. (2001). Stopping time: The genetics of fly and mouse circadian clocks. Annual Review of Neuroscience 24:1091-1119. [don't worry--the pages are short, and 8 of them are references]
**This paper is available on the web through university library subscriptions:** Medical School: www.ahsl.arizona.edu/journals/ejrnls/ Main Library: dizzy.library.arizona.edu/ej/ej.shtml#subscriptions You can access these electronic subscriptions from any U of A computer or, if you use dakota.com as your internet provider, from home.
WRITE:
Imagine that you have just obtained a large grant to fund circadian rhythm genetics research using your favorite experimental animal in your well-equiped lab. In 2-3 pages (see note below):
1. State the question regarding circadian rhythms you would most like to answer. (Advice: stick to questions that you think CAN be answered, but you need not restrict yourself to specific issues we have already discussed in class.)
2. Based on what we have read this semester, state the most likely answer to the above question (that is, your hypothesis).
3. Outline a set of experiments designed to test the hypothesis. As previously, state alternative outcomes depending on whether the hypothesis is true or false. Make sure to specify the experimental animal in which you will conduct the experiments.
Note: previous assignments have been 1-2 pages long. However, some of you are using such large margins and line spacings that little of substance is said in one page. Please keep this in mind. . . .

ECOL/MCB 320H: Honors Genetics

Overview

Format

Assessment and grading

Assignments

Latest assignment: Monday, December 3, 2001