Biology

[Veny]

Hello,
I am planning to do a science fair project on human biology, specifically focusing on cells. I was wondering what are some factors that can slow down or speed up cell division? Do these factors vary with the type of cells we are dealing with?

Thank you

[deleted-71791]

Hello Veny,

Thanks for your question. Congratulations on picking out an area to focus your science fair project!

This is a weighty but very interesting question, so we'll break it down. What we're looking at here is a question of why cells divide in the first place and what factors regulate cell cycles and cell division. Now, I'm assuming that you're familiar with the cell cycle itself (interphase with G1/S/G2, mitosis, cytokinesis). If not, you can check out these links for a refresher:

http://www.cellsalive.com/cell_cycle.htm
http://highered.mcgraw-hill.com/sites/0 ... works.html

Why do cells divide in the first place?
A cell will continue to grow until their need for resources becomes overwhelming or they experience difficulty moving nutrients and waste across their plasma membrane (the rate of transport slows because of cell volume). DNA overload also occurs where as the cell increases in size, it suffers an overwhelming amount of information and can not handle the volume. Division allows for replication of DNA material and decreasing volume.

What Factors Regulate Normal Cell Division and Cycles?
Various cells in the body have different growth rates: skin cells divide hourly, liver annually and nerve cells never divide. There are a variety of factors that signal to cells when to grow and when to stop. There are internal and external regulators. Internal regulators allow the cell cycle to proceed only once internal conditions and processes are met. What may interest you are external regulators. External regulators direct cells to speed up or slow down the cell cycle, or growth factors as they stimulate growth and division of cells. Contact with other cells is one, or Contact Inhibition. For example, when you get a papercut, your cells working to repair the area will quickly multiply until they reach the edges of the cut and then they stop. Molecules on the surface of neighboring cells also have the capability of causing cells to slow down or stop cell cycles, preventing excessive growth.

Growth signals to the cells depend on signal molecules, receptors, 2nd messenger molecules, cyclin nuclear proteins (or just cyclins) which concern themselves with normal cell division. An interesting area where you may be interested in directing your research is Cyclins, which regulate the timing of cell cycles in eukaryotic cells: http://en.wikipedia.org/wiki/Cyclin

A good set of resources to look at regarding the cell cycle and regulation include the following links:

http://www.biochemweb.org/cell_cycle.shtml
http://en.wikipedia.org/wiki/Cell_cycle
http://biology.kenyon.edu/courses/biol1 ... er_07.html

Gene Expression and Regulation
Now, these growth factors are products of genes (or rather their expression), and as you know contain instructions for controlling when cells grow, divide and die. Now, what we need to ask is what sort of cell division we're looking at: normal/healthy or abnormal/injury. The mechanisms and factors that affect both are not too different, but one (normal) is well regulated and controlled by the body while the other (abnormal) is when the body loses control of this process.

Normal cycles are regulated by Proto-oncogenes while abnormal ones are regulated by oncogenes, which can speed up cell division. Genes that slow down cell division or cause cells to die at the appropriate time are called tumor suppressor genes. Many scientists are currently working with areas such as cancer biology to understand DNA mutations (changes) that "turn on" oncogenes or "turn off" tumor suppressor genes. Cancer and other malfunctions of cell division are attributed to these DNA mutations where the cell may stop responding to external regulators or stop producing internal regulators. Aside from genetic factors, these genes can also be turned on and off by environmental factors (such as radiation, chemicals, viral infections, direct injury to the cells or organs via things like smoking and alcohol). Interesting, not all types of cells are suspectible to cancer (such as cardiac tissue/cells) which carries the thought that these factors do in fact vary with the type of cell one is working with.

A great talk on this is done by Eva Vertes of Princeton University: http://www.ted.com/index.php/talks/eva_ ... icine.html

Another good resource for a more complete looking into cell division and abnormal cell function is this document:
http://www.docstoc.com/docs/14975429/St ... and-Cancer

There are many great opportunities for a science project in this exciting area! Good luck in creating your project and hope this information will get you off to a great start in researching factors affecting cell division and growth and cell types.

-Melissa H.

[Veny]

Hi Melissa,

Thank you so much for your information. I found it all very interesting and helpful. I was reading the part on oncogenes, and I was wondering if there are partial oncogenes? In another words, can oncogenes be imbedded in a certain type of cell to mass replicated, but then take out the oncogenes before the cells turn into a tumor?

Once again, thanks so much

Veny

[deleted-71791]

Hi Veny,

Glad you found the information useful

To answer your question: Yes indeed, oncogenes can be embedded into cells and removed before the cell becomes a tumor. This is actually a part of genetics and molecular biology using site specific recombinase technology, or general recombinant DNA technology which allows for the manipulation and study of genetic material for gene function:

http://en.wikipedia.org/wiki/Site-speci ... technology

Essentially, this technology is used by scientists in the targeting of a specific sequence of DNA and splicing it with the help of an enzyme. They can then manipulate a variety of genetically modified organisms to control gene expression (in this case the oncogene), delete any undesired DNA sequences and modify the chromosomal architecture.

Specifically, you'd be interested in something called Cre-Lox Recombination which is used to establish tissue specific expression, allowing the isolation of individual genes and their functions. Cre-Lox can be used with virtually any type of cell as well which makes it a preferred technique because it is so versatile. You can select the area where and control at what level in which the gene will be expressed. Cre-Lox takes the oncogene and flanks it with a pair of lox-p sites (particular DNA sequences) and uses cre recombinase (enzyme) to splice it out later. So you could have this gene replicated in the cells multiple times, then splice it out and use for research without the cell becoming a tumor.

For more information on this technique, you can check out the following:

http://en.wikipedia.org/wiki/Cre-Lox_recombination
http://cre.jax.org/introduction.html
http://en.wikipedia.org/wiki/Cre_recombinase
http://www.bio.davidson.edu/COURSES/gen ... eLoxP.html
http://www.scq.ubc.ca/targeting-your-dn ... ox-system/

Hope this helps! Let me know if you have any further questions. And if you're interested in more on this, definitely check out a local university library or find textbooks on molecular/cellular biology and genetics to give you more depth on this topic. It's a lot to take in, but you're doing a great job with your critical thinking on the topic. A little basic cancer biology would also be useful to add to the reading

Cheers,
Melissa

[Veny]

Hi Melissa,
Cre-Lox Recombination is definitely a very interesting technology to manipulate DNA sequences. If it's so versatile, could it be used to correct or manipulate the disfunction of beta cells in diabetic patients? I have tried to do some research on my own for this topic, but the articles that came up were way too hard for me

Thanks,
Veny

[deleted-71791]

Hi Veny,

No worries. This is an advanced topic that even most undergraduate students won't encounter during their tenure at a university. However, don't be discouraged by it. I am impressed by your interest in the topic and would encourage you to check out these Science Buddies links on how to read a scientific paper and find and access academic sources:

How to Read: http://www.sciencebuddies.com/science-f ... aper.shtml
How to Find: http://www.sciencebuddies.com/science-f ... pers.shtml

To answer your question: Yes, there have been diabetes studies done using Cre-Lox for beta cells. For example:

http://physrev.physiology.org/cgi/conte ... /85/4/1255
Looks at the feasibility of regenerating and expanding beta-cell masses despite the body's low capacity for self-replication of these cells; use of Cre-Lox and application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others.

http://www.jbc.org/content/281/5/2649.a ... lltext=and
This one talks about a line of transgenic mice (genetically modified/spliced) called RIP-Cre that are glucose intolerant possibly due to absence of insulin secretion and using Cre-Lox to work with them.

http://www.ingentaconnect.com/content/c ... 0/art00002
Focused on establishing a human pancreatic beta cell line that can yield large amounts of cells for transplantation. Using Cre/loxP, they constructed a pancreatic beta cell clone.

There is a lot of opportunities for new knowledge and research in the field, and you may benefit from contacting a mentor who may be working in something similar to see if your area of research interest may correlate to something he/she is an expert in. You may also wish to speak with your science teacher in getting help and resources on this matter or finding a mentor (such as a university professor/researcher) versed in the topic: http://www.sciencebuddies.com/science-f ... tors.shtml

You may be interested in looking in the Science Buddies projects (and also the resources on the right sidebar) listing for a scaffold on which to build your science project and research:

Biotechnology: http://www.sciencebuddies.com/science-f ... ia=BioChem
Genetics & Genomics: http://www.sciencebuddies.com/science-f ... p?ia=Genom

I'd look at the following which seem to be according to your interests, especially the first one:

The Cancer Genome Anatomy Project: http://www.sciencebuddies.com/science-f ... t&from=TSW

DNA with a Restriction Enzyme: http://www.sciencebuddies.com/science-f ... g&from=TSW

Expression Cloning: http://www.sciencebuddies.com/science-f ... g&from=TSW

Take some time to look these over and see if one may be of interest to you in pursuing. If not, definitely look around for other types of projects at Science Buddies or work with your science teacher or mentor in designing one.

Hope this helps and good luck,
Melissa