Biology 446 - Unsolved Problems in Cell Biology - Fall 2013

Meets Monday, Wednesday and Friday, 10:00 AM-10:50 AM, Genome Sciences Building Room 1374.

Albert Harris:
Office 103 Wilson Hall; phone 919-966-1230
Home phone 919-493-1572 (Durham)

Office Hours: 11:00 to 1:00 Monday, Wednesday and Friday; 1:30-4:00 Friday, and by appointment



This year's topics for the Unsolved Problems course:

This course requires the equivalent of a term paper, which is due to be turned in no later than the week before Thanksgiving. How to write this paper is described below, under the topic "The Dreaded Erroneous Paper Report". You have to find a published research paper, the conclusions of which have turned out to be seriously wrong. That doesn't mean "fraudulent" and it also doesn't just mean that progress has shown the truth to be more complicated. Specific examples of appropriate papers will be discussed in class.

Wed. August 21: Philosophy of Science Assignment: Read this web page.

Fri. August 23: Assignment: Read the book "The Double Helix" by James Watson

Mon. August 26: Continue discussing the lessons of Watson's autobiography.


Wed. August 28: How the true cause of (most) ulcers got discovered: Lessons for you.

Wed. September 4: Begin autoimmunity

Monday September 9:

Wednesday September 11:

Friday September 13:

Monday September 16:

Assignment due Wednesday September 18:

Monday September 23:

Assignment due Friday October 4th:


Possible topics for the rest of the semester [posted October 4th]


Next assignment [posted October 9th]:

More things to think about [posted October 13th]:

a computer program to demonstrate the effects of applying force to an elastic membrane [posted October 14th]:

Follow-up on cytokinesis assignment [posted October 21st]:




It's About Time To Start Your Erroneous Paper Report [posted October 28th]


How to Cure Cancer [posted October 30th]


Cancer Chemotherapy [posted October 31st]


Interesting Article on the Cost of Drug Therapy [posted November 22]
Thanks to Stefanie Protasowicki for this link

Class notes on regeneration [posted November 22]

First set of review questions for the final exam [posted December 2]

Second set of review questions for the final exam [posted December 3]

No more questions will be added. [posted December 5]



#1) What goes wrong in the immune system, that causes autoimmune diseases?
   (Examples of autoimmune diseases are Multiple Sclerosis, Lupus Erythrematosus, Rheumatoid Arthritis and childhood Diabetes, and about 100 others.

For some unknown reason, the body fails to eliminate lymphocytes whose binding sites (of antibodies and T-cell receptors) fit the shape of certain normal proteins or other molecules, so that cells having these molecules get attacked.    Please note that everyone develops anti-self lymphocytes for all body molecules.

   But an unknown mechanism normally weeds out all anti-self lymphocytes.
   The mechanism of this selective "weeding-out" is not known.
   If you could discover this mechanism, and how to control it, that would be as big a breakthrough as Pasteur's invention of vaccination. (Yes, I know about Jenner.)

#2) How to use the many known abnormalities of cancer cells as the basis for new and more successful methods of chemotherapy.
   Cancer research is in a rut, with little progress in decades (despite propaganda).
   Cancer cells grow without control, not faster, than normal cells.
   Nevertheless almost all anti-cancer drugs target either mitosis or DNA synthesis,
   (Because of the old myth about cancer cells growing abnormally fast.)

   One unsolved problem is why these drugs work as well as they do;
   Maybe what kills cancer cells is not stopping at check points, despite damage?

   The subject needs bright young minds, like yours.

Some of the other topics that you can choose between:

#) Cell differentiation. How are certain subsets of genes "turned on" in each differentiated cell type? Why is differentiation usually irreversible?
Answer these questions, and stem cells will be obsolete.

#) The biophysics of embryonic shapes, especially skeleton and muscles.
(which happens to be my own research interest, but you don't have to choose it)

#) What is the cellular basis of memory? (A topic never covered before in this course, and that I am really not well enough qualified to present. But there are a lot of recent papers about this.
   Are memories encoded as changes in synaptic numbers? Or maybe changes in sensitivity of nerves.
   Resonance-like waves of coordinated electrical depolarization have recently been found.
   And we have some excellent neurological researchers nearby, whom we can ask.

#) Ossification and osteoporosis

Bone is a tightly woven mesh of two components: 1/3 type I collagen (protein); 2/3 crystallized calcium phosphate. ("mineral"). Although the collagen part is secreted by cells ("Osteocytes"), the mineral part precipitates outside these cells, by an unknown mechanism involving tiny vesicles.

Bone is constantly being re-dissolved and digested by acid and protein-digesting enzymes secreted by a special kind of multicellular macrophage (named an "osteoclast"). Bone somehow detects physical stress, and more bone is deposited (or maybe less is re-dissolved?) where stronger forces are imposed on bone. How bone detects forces (amount, location & direction)

Osteoporosis is the name for net loss of bone, either by too much dissolving or not enough depositing.

*Major unsolved problems include:
   *How bone detects forces (amount, location & direction)
   *How to cause more bone formation;
   *How those special vesicles cause calcium phosphate to accumulate into crystals
   *How to prevent osteoporosis.



some notes on grading, from a past year's course

The Dreaded Erroneous Research Paper Assignment