Cell Biology Exam 3

Answer all  three parts

Please keep the parts separate and put your name on the first page (at least) of each answer

Part 1. Dr Kim Creek



Your Ph.D. advisor is interested in transforming growth factor-beta (TGF-beta) signaling in cancer cells and has just obtained a pancreatic cancer cell line that no longer responds to TGF-beta (i.e., it is TGF-beta resistant). Your advisor wants you to determine how these cancer cells became resistant to TGF-beta. In no more than four double spaced type written pages first describe several different cellular and molecular mechanisms that cancer cells have utilized to become refractory to TGF-beta and then outline a series of experiments that one might use to determine exactly how the pancreatic cancer cells became TGF-beta resistant. It will be helpful to do some literature searching/reading to help you with this question.


 

Part 2. Dr Paul Housley

You are studying a new compound (“MoreDop”) which has activity in the brain. In particular, you have preliminary evidence that MoreDop causes the release of Dopamine from specific neurons in the hypothalamus. You obtain the following data from administering MoreDop to rats and measuring the release of Dopamine from the hypothalamus:

Dopamine released (pmoles)         MoreDop (mg)
100                                                     1000
100                                                     700
100                                                     300
90                                                       120
80                                                        80
70                                                        60
60                                                        50
50                                                        40
40                                                        30
30                                                        20
20                                                        13
10                                                         7
0                                                           3
0                                                           1




Question 1(50%):
What is the ED50 for hypothalamic dopamine release mediated by MoreDop? Show how you estimated this value.

A new synthetic compound (Estostim) exhibits appreciable estrogenic activity at doses of 10 mg or higher. Administration of Estostim to rats at varying doses up to 100 mg had NO effect on hypothalamic dopamine release. However, when 10 mg of Estostim is administered together with varying amounts of MoreDop, you obtain the following results:

Dopamine released (pmoles)       Estostim (10 mg) plus Indicated amount of MoreDop (mg)
100                                                    3000
100                                                    2000
100                                                    1600
90                                                       620
80                                                       400
70                                                       300
60                                                       250
50                                                       200
40                                                       152
30                                                       104
20                                                         64
10                                                         37
0                                                           16
0                                                             8


Question 2 (50%):
For this experiment, does Estostim act through the same receptor as MoreDop? What type of ligand is Estostim in this experiment? Show how you arrived at your explanations for this question.
 

Part 3. Dr Wayne Carver

You have generated data suggesting that the composition of the extracellular matrix can promote the differentiation of mesenchymal stem cells into cardiac myocytes. In these experiments, stem cells cultured within a 3-dimensional collagen type I matrix differentiate into beating cardiac myocytes while stem cells cultured in a laminin or other 3-dimensional matrix remain undifferentiated. Preliminary proteomics data suggest that the cells cultured in the collagen matrix express a unique protein that may be a novel matrix metalloprotease. You hypothesize that this putative protease is involved in collagen remodeling necessary for the differentiation of the stem cells into cardiac myocytes. Please discuss the features that you would expect this protein to have if it is indeed a matrix metalloprotease. Also, please briefly describe two experiments you could perform to test whether this protein in fact plays a role in the conversion of stem cells into cardiac myocytes.

This exam was posted Thursday November 26-29, 2007

It is due in the second week of January, 2007

Have a good holiday season and a happy New year