Dulguun Baasan

Dulguun Baasan 

2024-1 Geromics 

Geromics / BME80201

UNIST 2024-1

Dulguun Baasan / 20235360

SELF: Self Evaluating Learning Framework

“If I had a world of my own, everything would be nonsense. Nothing would be what it is, because everything would be what it isn’t. And contrary wise, what is, it wouldn’t be. And what it wouldn’t be, it would. You see? ”

- Lewis Carroll, Alice’s Adventures in Wonderland

Immortality has been one of the greatest mysteries of the world throughout the history. From powerful emperors to adventurous explorers, driven by their imagination, humankind has been looking for an answer to “cure” its mortal fate. This semester in Geromics class, I saw for the first time that aging can be not simply as an inevitable path rather a “disease” scientists are working to “cure”. From epigenetic reprogramming to telomere biology, I found a deep interest in Geromics and its connection to my research of DNA repair. Considering my growth in inspiration and knowledge as a biologist and attendance during the lectures, I am giving myself A.

In my SELF, I would like to highlight a scientist and his work in aging that influenced me the most this semester: Dr. David Sinclair. Dr. David Sinclair stated in his book, “Lifespan: Why We Age - and Why We Don’t Have To”, aging should be treated as a disease that can be slowed, stopped, or even reversed was evolutionary for me. First of all, it showed me that finding the ‘right” question and experiment design should be the most important quests in my research. Because he “established” aging as a disease, next steps would be to “cure” it. Steps of usual remedy for any disease is to quantify its damages, find the possible causes related with the damage, and develop methods to slow or stop it from each side. For the measurement, Horvarth clock was utilized. Dr. Horvath and his team’s epigenetic clock based on DNA methylation and later with environmental variants was used to “measure” aging so researchers can see changes in post anti-aging treatments. Furthermore, Dr. Sinclair stated “noises” of random and harmful changes in epigenetic marks are accumulated in cells that cells lose the their characteristics leading to aging and aging-related diseases. By using factors that induce pluripotency (Yamanaka factors), Sinclair lab showed cells can be reprogrammed to a moreyouthful and reversed aging. Currently, compounds such as resveratrol and NAD+ precursors are being studied further as potential pharmacological interventions for aging. From the other side, there are possible studies of gene therapy and biotechnology involving direct gene editing to modify the epigenetic marks. As I study DNA damages and their repair pathways, the epigenetic markers are indeed fascinating. It doesn’t change DNA itself but it can change multiple of it’s phenotypes and even involved in aging- one of the basic characteristics of the living. As the epigenetic open various doors and offer solutions as markers for previously “mysterious” phenomenons, it proves once more how complex the living is with its myriad of simultaneous biochemical reactions. The era of epigenetic has started already and even though scientists are advancing in the field actively, there are many more to be answered such as how to use these markers to diagnose any related diseases efficiently and how to “safely” and “ethically” dive into steps of “immortality”. Lastly, as I quoted one of my favorite lines from author Lewis Carroll in the opening, nothing can be what it is. Your perspective and questions define your world and Geromics and Omits classes at UNIST challenged me to take science personally. The examples of research such as from Dr. Sinclair or Dr. Blackburn or Dr. Bhak showed me even though science and research search for the universal truth yet how to approach the questions is one of the most intimate and personalexpressions of the scientist. With continues growth and curiosity with pinch of personal “nonsense” in the world, I will continue with my pathway as a researcher.

2023-2 Omics 

Research Area : DNA maintenance and genomic integrity, cancer biology, genetic and molecular studies of cancer 

Current Project : 
1. Characterizing relationship between DNA double strand break (DSB) repair pathways
2. How does theta-mediated end-joing (TMEJ) repair DSB in M phase? 
3. Developing reporter assay system to monitor TMEJ repair 
 

SELF 

  Dulguun Through the Looking Glass: rise of the new perspectives in Omics class 

 

 

Standing on accumulation of knowledge and exploration of the past “natural history” and “natural philosophy and physiology”, modern day “biology” was born in 18th century. As the purpose and demand to study living organisms expanded, the technology and methods advanced accordingly which brought today’s  intersection between thought and data driven branches of biology. While discovery of deoxyribonucleic acid (DNA) structure enabled scientists to answer their hypothesis on genetics and evolution,  the establishment of -omics gave opportunities to bring refined hypothesis based on vast amount of data. Being trained as experimental molecular biologist and through the looking glass of Omics class, I aimed to further investigate the current states of both fields and ways to integrate them for my research interest. After analyzing various sources of literature and discussion together with my research experience, my perspectives were expanded in systems biology, cancer epigenetic, and aging research. Additionally, the Omics class taught me the importance of concise scientific communication and confidence in my learning methods. 

Based on my growth in critical questioning abilities and scientific knowledge, I am evaluating myself with grade A. 

 

1. Defining the approach : Selfish Gene vs Systems Biology

Popularized by Dr.Richard Dawkins, “selfish gene” is a concept that genes are driving force behind natural selection and organisms are essentially “survival machines”. The gene-centric view can be seen as reductionist, focusing on the smallest unit to explain the complexity of biological phenomena. On the other hand, Dennis Noble states genes are important, but integrative and systems biology are equally essential. Systems biology view supports more holistic approach to look at interactions and dynamics of entire systems. 

As my current research interest revolves around DNA repair, it is crucial for me to define my approach on perceiving the bigger picture. Aside from storing and passing essential genetic instructions, DNA ensures continuity of life through its guidance on protein synthesis and maintenance of genomic integrity. Thus, I believed understanding smallest unit can explain the characteristics of complex organisms which led my ultimate interest to study DNA repair. DNA double strand break (DSB) is one of the most cytotoxic damages in cells that timely repair is processed through three different pathways of homologous recombination (HR), non-homologous end joining (NHEJ), and microhomolohy mediated end joining (MMEJ). Among the three, I focus on understanding MMEJ which was originally discovered  as “backup” pathway due to its infrequent and error prone repair nature. Emerging studies now suggest MMEJ is main repair pathway in mitosis yet it is still not clear whether it suppresses or promotes cancer.  I wondered if the gene “chooses” MMEJ to repair itself to continue its survival regardless of the possibilities of damages it can put on the  cell— the system, gene is clearly more “important” than the organism. This evidence supports “selfish gene” concept where survival of the gene is essential and driving force for biological phenomena.  

However, during Omics class I understood it can be explained otherwise. From systems view, cells choose to have MMEJ in M phase, HR in G2 and S phase and NHEJ in G1 phase indicating cell has definitive order that allows its survival in all stages of  its life. Unrepaired damages will pass each phase to be corrected which shows the survival of the system is more complex than gene. Moreover, our class discussion prompted me to read Siddhartha Mukherjee’s “Song of the Cell” where the author discusses details of  intricate connection between cells in development and genetics. Mukherjee’s discussion further supported cells or systems together play essential role in organisms not only gene. Furthermore, Omics class discussion on the emerging studies of bioinformatics in epigenetic markers showed environmental factors affect an organism as equally as its gene. Lastly, from view of evolution, Yaneer Bar-Yam’s argument against Dawkins’ “rower analogy” and  mathematical model demonstrating “selfish gene” as not consistent approximation persuaded me that view of systems biology has more evidence. Thus, I believe “selfish gene” concept has several flaws that system biology can explain.  

 

1. Defining the tool: What is DNA? 

With the perception of biology as systems, then I investigated further to define what is DNA in different branches of biological research. In molecular biology, DNA is a double helix nucleotide base structure that “codes” organism’s genetics. Changes in DNA can regulate protein levels that can lead to disease and cancer development. DNA replicates, responds and repairs. DNA interacts with proteins and gets regulated. However, in Omics, DNA is combination of 4 letter that “codes” organism’s genetics. Genetic and genomic data can be “read” as large sets of data and can be mined for patterns and anomalies. DNA data mining can be used for genomic sequence analysis, variant analysis, association studies, pharmacogenomics, population genetics, disease biomarker discovery, and precision medicine. Omics is sum of interconnected fields and often used in combination to obtain more comprehensive understanding of biological systems. Omics class introduced and ignited my interest in possibilities of  wide range and  high throughout approach to study DNA. 

 

III.  Defining the design: What is next? 

Based on my experience during the semester, for my next project I would like to investigate DNA damage in blood. More specifically, I am interested in genotoxic aldehydes in hematopoietic system. Recent studies show that simple aldehydes produced as byproduct of metabolism can attack DNA. Moreover, genotoxic aldehydes in hematopoietic stem cells (HSCs) cause accelerated aging and blood production. However, it is still unclear how certain DNA damages and metabolites in blood can affect aging and cancer. Aside from conducting conventional experimental assays, I want to study blood DNA damage as cancer and aging markers from omics and systems view. 

 

IV. SELF: Self Evaluating Learning Framework

Based on my learning during Omics class, I evaluated myself with A. I invented 5 evaluation criteria for myself: developing interest—attention,  gaining new insight,  connecting information  through inside and outside class,  engaging and exchanging critical thinking, and understanding others’ point.  I have participated in each class discussion, presented my current research progress, developed and learned new interest in data driven science, and planned new individual project for myself based on what I learned.  However, I am not fully satisfied with my lack of understanding on others’ research topic which led to me deduct some points. In the future, I am aiming to become a scientist with strong background in fundamental research sciences that can be able to communicate current topics fluently.