Episode 13: We have the Number ONE Methods

When you see that extra long Ashwath Blog Post

Before I start my blog today, I want to explicate the slight change to my methods. Previously, the regions that I selected for analysis were chosen based on so called "proven mutations." I confused myself on the selection of the regions.

First of all here is here is the breakdown. When something evolves, normally you wouldn't expect the vestigial structures to matter much in everyday function. For example, if the genetic code of your tail bone was altered, you would not expect it to change the function of your overall body because your tail bone is not important to your structure (technical term: non-conserved). In a protein, a non conserved region is usually identified by a lack of change in structure. In general, these non conserved areas have very little effect on the structure of the molecule. If I had a red Lego brick tower, and I swapped one of the red bricks with a yellow one. You would expect that the tower would still stand because all I did was swap a brick with a similar one. That is what has been assumed in the protein research field. To put it in the context, Lac 1 is made of 3 regions (I'll name and explicate them in a revised version of my methods), 2 of these regions are conserved but the third region is non-conserved. If I swapped the third region with a code similar in structure, one would expect that the new region would not change the function of the protein because the structure is not changed. However, new research from Professor Swint-Kruse, has shown that these non-conserved regions actually matter in the function of the molecule, even if they do not affect the structure. But Professor Swint-Kruse only identified this discrepancy, she did not provide an analysis or explanation for her findings. That's where the gap is. I will use Lac1, the protein that she analyzed, and replicate her trials and protein models. But I will use the DFI analysis to explain the change in function by analyzing the dynamics of the protein. I will be looking at the interactions between each amino acid, looking further beyond the normal structural and functional analysis. The mutations I will use will maintain the conserved parts of Lac1, while changing the non-conserved structures to structurally similar structures from like Galactose1 and Fructose1 in order to see the differences in dynamic interactions.

Akash when he hears the instruction to close the door

Let me explain it again with another analogy. Mrs. Haag is telling me to close the door, so I get up and close the door. Now we swap me with Akash, who speaks a foreign language. Structurally, Akash and I are similar, so we would expect Akash to close the door. But Akash can't close the door because he can't understand English. He can't interact with Mrs. Haag properly, so the function of closing the door is impeded. In proteins, I want to find the why for the disfunction. Or in this case, find out that Akash, though structurally similar, cannot understand English.


The biggest weaknesses in my methods are 1. Explication, 2. Purpose of the Paper, and 3. DFI-analysis. As the large explanation above shows, I must ensure that all parts of my methods are understandable and justified. So far I have only talked about the side-benefits of my analysis, but I was finally able to put together the final picture shown above. Hopefully, I have explained it thoroughly enough. i will add it to my methods and lit review as necessary (not huge changes, but clarifies the project overall). Honestly, its almost like my excitement about my project has been renewed because I discovered a new purpose to my research, so I'm happy to delve into my project once again! The selection and preparation of my materials are solid. The biggest limiting factor is DFI-analysis. In the papers I have read, I have only been able to see the explanation of DFI and the results from DFI. I currently have not been able to interact with the DFI program to thoroughly understand and explain its inter-workings. This is the biggest unfixable problem that can only be solved by running the trials myself.

The main concern for me is my explication of the technical terms. I double-checked with Mrs. Haag and made sure that everything vague or assumed was explained in the methodology. But Mrs. Haag has been working with me on my project for a while now, so there might be assumed knowledge. This is one of the main weaknesses of my methods.

Overall, I am combining the DFI method from Dr. Ozkan, with an investigation of Lac1 first found by Professor Swint-Kruse. The strength of the scientific nature of the methods are certainly there, but I believe that my explanation is the key to success.

And of course I have not forgotten the meme of the week boys. It's We are Number One. This internet sensation has not only raised enough money to give a man cancer treatment, but is also light hearted and genuinely funny. The title of the videos found start with We are Number One BUT ... Then something is changed in the video.

Here is the Original:
https://www.youtube.com/watch?v=PfYnvDL0Qcw

Here is one of my favorite meme versions: We are number one but "we are number one" is replaced with Gordon Ramsay insults

https://www.youtube.com/watch?v=qEkH9BF0sKw