Help with Peer Review

This is my Statement of Purpose for this.  Since I’m still unemployed as a doctor, I am trying to find any means of survival, but in the meantime this has always been more of a dream of mine: to save the world!  So please read my Statement of Purpose and hope that you can give CONSTRUCTIVE criticisms (not just criticisms, give suggestions!) on creating the best Statement of Purpose ever!

Statement of Purpose
Muhammad Zeitsev bin Azman, MD BSc

The Introduction

“How do histones know when to dissociate from DNA so that transcription of specific sequences can happen?”

This was the question I posed in 2000, intriguing my advance genetics professor at North Carolina State University. Ever since then, I always wondered what controlled intracellular events to maintain a nearly perfect system that feeds from its surroundings, grows into a self-sustaining organism, recycles its own waste products, and times itself to terminate. Being a beginner in my biochemistry degree, I could only make educated speculations on how things occurred within the cell. As I continued my education in the field of biochemistry, genetics and human physiology, I started realizing there is a vast unknown of cellular activity that, despite cramming known knowledge into my brain, is still unexplored and unexplained.

The Interest

I was always fascinated in the possibilities of biochemical research, from protein structures to intracellular systems to intercellular communication. After learning about the basics of cellular signaling in my third year, it dawned to me that our own symbiotic multicellular system works very similarly to the ecological environment that we live in. Thus any event happening in the system can be traced back to a single trigger. This might be a broad explanation into what I theorize is the cause of many diseases, and it is also my “canned response” to a lot of bar conversations on how society or organisms work, but is a good basis of research as long as the details leading up to these events have been compensated for and studied.

Since I believe there is a reason to everything, I became adamant in how to reverse engineer the cellular system to see how cells are triggered to either perform seemingly miraculous acts, or to become detrimental to itself, its immediate neighbors, and to the organism as a whole. However, I needed to expand my knowledge and after my brief stint working in clinical trials, I decided to further pursue a medical degree.

Learning human medicine, while trying to understand roles of individual cells and how its immediate communication can affect the organism as a whole, is analogous to looking at the world and trying to understand why someone in NYC is buying a snow cone in the middle of winter for his wife, who would eventually give birth to a child that would be the scientist which revolutionizes global healthcare. Although it deepened my understanding of how individual cells make up the organ systems that forms the organism, I lost the sense of understanding the intracellular communication that happens within the cell that triggers those very cellular events that can cause harm to the entire organism!

During my medical education, I became attracted to the subject of cancer. Some people joked that I might cure cancer one day, but that day is not far off. With advances in understanding some cellular triggers, links between DNA to protein (and vice versa), and communication between cells in organisms and organ systems, therapies based on monoclonal antibodies have been created that are able to bind specific cells, labeling them for destruction. That is very exciting! However the question remains of why some people (albeit few), who still have HER2 expression for breast cancer, do not get breast cancer? Or why do many farmers who smoke since they were twelve live until the overripe old age of 90 years?

I believe and theorize that those cells which cause harm need to be initially triggered, and some genetic-based, double-knockout triggers have already been discovered. However, those triggers have their own intracellular causes which initiate the expression of unwanted genes that can harm the cell itself, its neighbors, organ systems, and eventually the entire organism. I find the similarities within human populations. When someone is stressed and has a bad day, they might affect the next person they meet. That woman then goes home and feel stressed about the horrible person that she met, and although her marriage is apparently symbiotic with her husband, she yells at him. He then never buys her that snow cone to make her happy. She then slightly changes as a person, as the scale of symbiosis tips, and everything that he does has a negative connotation on her. Eventually, she hits her critical concentration of stress, and leaves him to marry another man, and never births that child who will save global healthcare.

The Summary

This sequence of events might be a little psychologically far-fetched, but I have known people who have had a greater negative reaction to a lesser critical concentration of stress. This is much like the sequence of cellular communication that happens within the cell to either cause it to undergo apoptosis, or to finally make an error and cause a tumor or cancer. I believe and aim to research that, at the intracellular level, individual stressors at high enough concentration is the trigger to cause specific DNA expression. It might be too simple to just categorize cellular responses to the environment based on primary, secondary and tertiary cell signaling methods. I believe cell response is based on fluctuating concentrations of intracellular proteins, creating a fine balance to maintain cellular biostasis. Being a biochemist, chemist, medical doctor and a minority member of a relatively conservative society, I find that in order to get a message through to change a system, many people with the same message must be involved to amass to that critical concentration which creates a shift in paradigms.

Therefore I find the research being done with Călin Guet or Tobias Bollenbach crucial in understanding the beginnings of cellular response to environmental and internal stressors, which could be the key in resolving many medically known diseases. What I propose to bring to the group is the possible understanding of the triggers, and the effects of critical concentration of these triggers to DNA response and expression within these individual cells.


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