Dulguun Baasan
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 the accumulation of knowledge and exploration in the fields of “natural history” and “natural philosophy and physiology”, modern day “biology” was born in the 18th century. As the purpose and demand to study living organisms expanded, the technology and methods advanced accordingly, which brought on today’s intersection between thought and data-driven branches of biology. While the discovery of deoxyribonucleic acid (DNA) structure enabled scientists to answer their hypotheses on genetics and evolution, the establishment of -omics gave opportunities to develop refined hypotheses based on vast amounts of data. Trained as an experimental molecular biologist and through the looking glass of the 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, I expanded perspectives 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 A0.
Contents
I. Defining the approach : Selfish Gene vs Systems Biology
Popularized by Dr.Richard Dawkins, “selfish gene” is a concept that genes are the 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 that while genes are important, integrative and systems biology are equally essential. The Systems biology view supports a 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 the 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, the timely repair of which is processed through three different pathways: homologous recombination (HR), non-homologous end joining (NHEJ), and microhomology 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 the main repair pathway in mitosis, yet it is still not clear whether it suppresses or promotes cancer. I wondered if the gene “chooses” the MMEJ pathway to repair itself to continue its survival regardless of the possibilities of damage it can put on the cell— the system, the gene is clearly more “important” than the organism. This evidence supports the “selfish gene” concept where survival of the gene is an essential and driving force for biological phenomena.
However, during the Omics class I understood it can be explained otherwise. From a systems view, cells choose to have MMEJ in M phase, HR in G2 and S phase and NHEJ in G1 phase, indicating that the 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 a gene. Moreover, our class discussion prompted me to read Siddhartha Mukherjee’s “Song of the Cell” where the author discusses details of the intricate connection between cells in development and genetics. Mukherjee’s discussion further supported that cells or systems together play an essential role in organisms, not only genes. 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 the 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 the view of systems biology has more evidence. Thus, I believe the “selfish gene” concept has several flaws that system biology can explain.
II. 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 a combination of 4 letters that “code” an 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 a sum of interconnected fields and often used in combination to obtain a more comprehensive understanding of biological systems. Omics class introduced and ignited my interest in possibilities of a 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 a hematopoietic system. Recent studies show that simple aldehydes produced as a 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 an “A0” grade. 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’ points. I have participated in each class discussion, presented my current research progress, developed and learned a new interest in data driven science, and planned new individual projects for myself based on what I learned. However, I am not fully satisfied with my lack of understanding on others’ research topics which led me to deduct some points. In the future, I am aiming to become a scientist with a strong background in fundamental research sciences that can be able to communicate current topics fluently.