Proposal Placed in Dropbox. The link is http://dl.dropbox.com/u/11745574/Proposal---Aptamer%20Stream%20%28September%202010%29%207.docx
Figure 1:http://en.wikipedia.org/wiki/File:Protein_SATB1_PDB_1yse.pngIn vitro studies that have been conducted showed a reduction in SATB1 expression in highly metastatic cell lines reduced the invasiveness of those cells as well as their capability for unattached growth. Aggressive cancer cells need unattached growth in order for them to move through the blood and lymph vessels. (2) This in fact proves that the inhabiting of SATB1 will hinder it from increasing the growth of aggressive cancer tumors. There are no known successful aptamers that have been developed as therapeutics against SATB1.
An aptamer if successful would be very useful as a therapeutic against the SATB1 protein. Inhibiting the functional pathway of SATB1 would prevent its reprogramming of the genome to change the expression of genes that encourage the metastasizing of breast cancer cells. With that said, the aim is to develop an aptamer with a high enough affinity of specificity to bind to SATB1 in order to prevent it from being a “master regulator”. Like most anti-cancer drugs any therapeutic development against SATB1 expressed by breast cancer cells will also have an adverse effect on normal cells. Researching what types of cells are likely to express SATB1 could be useful in terms of a preventative measure. In vitro selection would be the method used to select against SATB1. Figure 2 is an outline of what is discussed in this abstract.
FIGURE 2) When Breast cancer cells express SATB1 protein, SATB1 reorganizes hundreds of genes thereby leading to the metastasizing of breast cancer cells. The inhibiting of SATB1 could prevent this from happening.
7 comments:
Good progression of background information, but possibly a little lengthy. I like the consideration of adverse effects to inhibition, and would be interested to see those findings/related articles in the proposal. I would make some revisions by removing the personal identification (eg. "Through my research, "I have to figure out..") and possibly reorganize some sentences that sound redundant ("can therefore bind to cells and reorganize the genes and therefore allow for metastasizing").
Thank you for you advice Holli! I have revised the first person speaking and I am still going through reorganizing the sentences that sound redundant. The abstract is lengthy but I am having trouble knowing what to cut out. I want it to be shorter but fear that a reader might leave feeling as though they are missing something.
Lola, This abstract is only lengthy because you explain everything in the first figure. SATB1 sounds like an interesting target if for no other reason than it binds dsDNA! We could do a very easy dsDNA selection if you can find the target commercially. Here are some comments:
1.) In most instances, you should not be quoting the original author. Reword the essence of what they say and then reference them. You only really use quotes when it is something important they said. For instance, if you want to talk about part of a speech MLK Jr said you would quote it then discuss it. If you want to talk about what someone said, you would quote it and then talk about it. You don't generally just quote basic information from an author unless you are writing a news piece (such as the authors were doing from whom you took quotes from).
2.) Why does it matter, or how can it be that "The gene is composed of chromatin, nuclear heterochromatin, nuclear matrix and a nucleus"? The structure of the gene may be wrapped in this stuff, but the gene doesn't encode this stuff does it?
3.) The target link at the bottom from Santa Cruz was for the siRNA and not the protein target. SATB1 antibodies are plentiful, and the blocking peptide for those antibodies are available. The problem with the blocking peptide is it is not available as a conjugate. Therefore, some product will be lost when taggin/purifying. But I did find it from ProSci, Cat# 4631P, $70 for 50ug and it is only 15 amino acids so it is small and therefore the weight will go a long way.
Hey, great idea! I was wondering if this aptamer would be for the permanent inhibition or if it would be part of a dosage therapy plan? Does the body continually produce SATB1? Or is it present in limited dosages, i.e. those who have more of it are more prone to breast cancer?
Good start.
Please take a stab at rewriting your introduction. There's a lot of information, but I think it can be condensed. One of my tricks for rewriting documents is to hide the document away & try to rewrite it from scratch without referencing the old draft. I'm always amazed at how much extra (& often unnecessary) stuff is omitted when I do that.
The last paragraph is a bit unclear to me. Are you just saying that the aptamer will have a therapeutic application, but there's a chance it could be harmful to normal cells? Aren't most anti-cancer drugs harmful to normal cells? How do others deal with the problem? I'm thinking some good cells will die with the bad, but that's the way it goes. I wouldn't worry about going into detail here. Just say something about the potential toxicity of the aptamer against healthy cells expressing the protein.
Lola,
I just got a response from ProSci. The sequence of the immunogenic peptide is: C-ASPAESDEENRQKTR. Can you use BLAST to find out where on SATB1 this actually is? I think it is closer to the C terminal end. When you find it, compare to the location of the DNA binding domain of the protein. As we talked about, I doubt this peptide can actually binding DNA, but since it is immunogenic, it is likely exposed and therefore any aptamers selected against it will also bind to full SATB1.
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