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ACADEMIC CONTRACT FOR INDIVIDUALIZED STUDY
DIRECTIONS: Contracts are due by October 18 for Exploration Term 2014, February 18 for Spring Term 2014, and May 16 for
Summer Term 2014. Contracts must be typed. Print one copy to be signed by individuals listed at the bottom. Submit the
original, signed form to the Office of Exploration Term and Contract Learning (Norton 262). Incomplete contracts will not be
accepted. Your contract will be reviewed by the ECL Committee for approval.
TERM TO BE REGISTERED: Exploration Term
FOR OFFICE USE ONLY
STUDENT’S NAME:
PHONE NUMBER:
CAMPUS BOX NUMBER:
BSC E-MAIL ADDRESS:
STUDENT ID:
HOME ADDRESS:
CLASS LEVEL: Senior
COURSE PREFIX AND NUMBER: BI 499
NUMBER OF UNITS: 1
PROJECT SPONSOR:
FORM OF GRADE: S/U ( )
LETTER ( x )
I.
State the title of the project: Developing a yeast model to study the chemotherapeutic drug Navelbine
II.
Give a general description of the project. Summarize your project in two sentences or less:
Navilbine (Vinorelbine) is a chemotherapy drug that is given as a treatment for some types of cancer including breast
cancer and non-small cell lung cancer. There are few good model systems available to study navelbine. The purpose of
this project is to develop a yeast model in order to understand the mechanism of navelbine toxicity and how cells become
resistant to navelbine.
III.
State the learning outcomes of the project:
The primary focus of this project is to confirm that the taxol sensitive yeast strain created by Gupta et. Al. (2003) is also
sensitive to navilbine. Once the yeast model has been created, the next objective will be to understand which drug pumps
confer resistance to navilbine in cells. The last objective will be to see if the compound previously shown to inhibit some
types of drug pumps can reverse resistance to navilbine.
IV.
Give the general methodology. Summarize for the Committee how you will achieve the objectives listed above. Include
evidence of approximately 150 clock hours of in- and out-of-class involvement.
The project will begin by obtaining the taxol sensitive yeast and treating it with navilbine to confirm sensitivity to the
drug. Next, the taxol sensitive strain will be transformed with a hypermorphic allele of PDR3 which regulates expression
of many proteins that pump drugs out of cells. By selectively deleting some of these drug pump genes, the ones
responsible for resistance will be identified. Resistant strains will also be treated with the inhibitors OC-144-093,
LY33579, and MS-209 in order to learn which inhibitors can restore the toxicity of navelbine. 30-40 hours per week will
be spent in the lab.
If this is an internship, give the name, full address, and email address for off-campus agency and supervisor:
V.
Describe the academic component of the project:
A.
List required readings and resources for the project (in full citation format):
Adams, DJ., VC Knick. (1995) P-Glycoprotein medicated resistance to 5’ nor-anhydro-vinblastine (Navelbine).
Invest New Drugs. 13, 13-21.
Cardenas, Maria E., Christine Cruz, Maurizo Del Poeta, Namjin Chung, John R. Perfect, Joseph Heitman. (1999)
Antifungal activities of antineoplastic agents; Saccharomyces cerevisiae as a model system to study drug action.
Clinical Microbiology Reviews. 12, 583-611.
Gupta, ML Jr., CJ Bode, GI Georg, RH Himes. (2003) Understanding tubulin-Taxol interactions: mutations that
impart Taxol binding to yeast tubulin. Proc Natl Acad Sci U S A. 100, 6394-6397.
Kimura, Y., J Aoki, M Kohno, H Ooka, T Tsuruo, O Nakanishi. (2002) P-Glycoprotein inhibition by the
multidrug resistance reversing agent MS-209 enhances bioavailability and antitumor efficacy of orally
administered paclitaxel. Cancer Chemother Pharmocal. 49. 322-328.
Newman, MJ., JC Rodarte, KD Benbatoul, SJ Romano, C Zhang, S Krane, EJ Morgan, RT Uyeda, R Dixon, ES
Guns, LD Mayer. (2000) Discovery and characterization of OC144-093, a novel inhibitor of P-glycoproteinmediated multidrug resistance. Cancer Res. 60, 2964-2972.
Shepard, R.L., J. Cao, J.J. Starling, A.H. Dantzig. (2003) Modulation of P-glycoprotein but not MRPI (or BCRP)
medicated drug resistance by LY33579. Int. J. Cancer. 103, 121-125.
Perego, Paola. Gretchen S. Jimenez, Laura Gatti, Stephen B. Howell, Franco Zunino. (2000). Yeast Mutants as a
model system for identification of determinants of chemosensitivity. Pharmacological Review, 52. 477-491.
Pereira, E., J. Tarasuik, A. Garnier-Suillerot. (1998). Kinetic analysis in living cells of the inhibition of the Pglycoprotein medicated efflux of anthracyclines by vince alkaloids. Chem Biol Interact. 114, 61-76.
B.
Describe the academic product to be evaluated (e.g., oral or written examinations, research papers
and their length, analytic journals, works of art, performances, etc.):
An oral presentation on Honor’s Day and a 15-page scientific paper
SIGNED BY:
STUDENT:
DATE:
*FACULTY CONTRACT SPONSOR:
DATE:
*FACULTY ADVISOR:
DATE:
*DEPARTMENT CHAIR:
DATE:
ECL COMMITTEE:
DATE:
*In the event all three are the same individual, you must obtain a signature from a faculty member in the same department other
than the Department Chair.