[DIYbio] Re: Intein control in a targeted cancer therapy

Hello...

I wrote "it isn't the function of the protein product that is necessarily altered ".  I don't believe that implies that there are no exceptions.  As to the quote from Wiki... I agree, the sentence needs to be corrected... and yes, of course, I know that ubiquitination is on the Omega end and transcription is on the Alpha, but the general sense of the text conveys that cancer is a disease of de-regulation, whether that be of expression or removal of activity control.

This is just one example, but it's far reaching…

--"MYC was among the first oncogenes to be identified, and its deregulated expression is widespread in human cancer (Vita and Henriksson 2006)."


Oncogene addiction: setting the stage for molecularly targeted cancer therapy

Sreenath V. Sharma and Jeffrey Settleman

On activity, regarding BCR-ABL, Sharma and Settleman write "The ABL and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, which are targets of imatinib, are often activated by chromosomal translocations (BCR-ABL, TEL-ABL, TEL-PDGFR).


I disagree that a change resulting in constitutive activation of a protein that previously wasn't constitutes a change in function.  If a protein phosphorylates, that is its function, whether it needs requires a reaction or not.  I do agree, of course, that this change has nothing to do with transcription of its gene.  However, that change is a change in the overall regulation of the cell.


------------------

I would be very happy to get my paper before a peer review, as that was a suggestion made by others.  However, I've contacted several, including PlosOne and all but one said no outright because I wasn't a member of a lab or employed by a pharma.  The one exception was the new journal from Nature Publishing... they agreed to fund the peer review for me, however, I have yet to hear a reason for rejection even though it was due to complete almost 2 months ago.  My attempts to contact one of the reviewers have been rejected.


As to my article that was published... I co-wrote that with a former Pfizer senior scientist and adjunct professor at U Conn (who has presented at the New York Academy of Science). I didn't know much about how journals and peer review worked at the time and I believe they were doing what they could to start a new journal.  I was asked to co-author the article so I did.

----------------------

 As to protein structure…


"Directed evolution circumvents our profound ignorance of how a protein's sequence encodes its function by using iterative rounds of random mutation and artificial selection to discover new and useful proteins.

Notwithstanding significant advances, a molecular-level understanding of why one protein performs a certain task better than another remains elusive.

Thus predicting the amino acid sequence, or changes to an amino acid sequence, that would generate a specific behavior remains a challenge, particularly for applications requiring high performance (such as an industrial enzyme or a therapeutic protein). Unfortunately, where function is concerned, details matter, and we just don't understand the details."


- Exploring protein fitness landscapes by directed evolution

Philip A. Romero

Frances H. Arnold  (CAL Tech)



On Monday, July 1, 2013 4:47:47 PM UTC-4, Mackenzie Cowell wrote:

Passing your message on to the main list, Scott.

---------- Forwarded message ----------
From: Scott Tarone <sta...@synapticsynthase.com>
Date: Sun, Jun 30, 2013 at 7:16 PM
Subject: Intein control in a targeted cancer therapy
To: con...@diybio.org


Hello,

 

I'm not sure if your group is the right place for me to look for help, but I thought it worth a shot.

 

I am self-taught in the biosciences… Neuroscience, Genetics, Immunology, and Targeted Cancer Therapies.  After watching a presentation on Chimeric Antigen Receptors on the NIH site, I had an idea on another approach that would remove the limitations inherent in the technique presented (though it was a fantastic step forward, and very successful).  My approach is based on a constitutively active Caspase 3 mutant controlled by a molecular switch.

 

Long story short… I just wrote up a few paragraphs on my idea and sent it off to a few people in the field.  One of them (a senior scientist from Pfizer) got back to me a few months later and said I may be on to something and that I needed to write a paper.  I did  that and then wrote an article on that paper with him and that was published in a small time online journal last year.  Since then my paper and the article have been download several hundred times.

 

I didn't provide the links or an attachment as my first attempt to send this email was blocked by spam filters.. I will provide that information if you have interest.  In the interim, you can search for "intracellular Caspase modulating Chimeric Antigen Receptor".

 

Thank you very much for your time…

 

Take care,

Scott

 


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