Tuesday, September 3, 2024

A Brief Introduction to Molecular Biology

 

In October to November 1991, I attended the Fifth Asian Course in Tropical Epidemiology under the Southeast Asian Ministers of Education Organization (SEMEO)Technical Cooperation jointly held among the National Centre for Malaysia SEAMO Topical Medicine and Public Health Project and the Institute for Medical Research in Kuala Lumpur in collaboration with the German Agency for Technical Cooperation. It was held at the Institute for Medical Research where I worked. Prior to that I also attended another postgraduate in-service course in biotechnology and molecular biology. 

These postgraduate courses were meant for senior medical officers and senior medical researchers. They were in-service courses meant for them  

In those days, knowledge in these areas, especially in molecular biology and molecular medicine, wasn’t very advanced yet with few discoveries and their applications.

Years on I picked up on where I left to gain more knowledge on molecular biology and its applications in molecular medicine. Clinical medicine as practiced in hospitals as a standard routine is very boring to us with very slow advancement  

So today, based on what I have gained in my previous training, let me write a brief essay on molecular biology first, and separately in another essay, I shall write on how molecular biology is used and applied for the advancement of medicine in several areas, from diagnostics, development of new drugs to new treatment of diseases.

But first, let me deal with molecular biology as a springboard before we go into its application in medicine.

Molecular biology is a branch of biology that focuses on the molecular underpinnings of biological activity. It involves the study of the structure, function, and interactions of biomolecules, such as DNA, RNA, proteins, and other macromolecules, which are essential for life processes. The field intersects with genetics, biochemistry, and cell biology, and has vast applications in medicine, biotechnology, and environmental science.

What then are the key areas in the study of molecular biology?  The first fundamental area is on DNA and RNA structure and function. We can broadly divide this into 3 areas, namely, DNA replication and repair based on studies of how DNA is copied and repaired in cells. For example, research into DNA polymerase enzymes that are responsible for DNA replication has provided insights into the accuracy of genetic information transfer.

The second area we go into is transcription and translation. This focuses on how genetic information is transcribed from DNA to RNA and then translated into proteins. The central dogma of molecular biology, which describes this process, is a fundamental concept.

Then thirdly we go into gene regulation that involves our understanding how genes are turned on or off in response to different stimuli. The discovery of regulatory elements like promoters, enhancers, and silencers has deepened our understanding of gene expression.

Having understood these 3 basics, we can then go into protein structure and function. Again, there will be 3 basic ideas. The first will be on enzyme kinetics. These are studies on how enzymes catalyse biochemical reactions. The Michaelis-Menten equation is a key model used to describe enzyme kinetics. Having understood its mechanism, we can now proceed to protein folding where studies show us how proteins fold into their functional three-dimensional shapes. Misfolded proteins are linked to diseases such as Alzheimer's and Parkinson's.

Next in line is our understanding of post-translational modifications. This area examines how proteins are chemically modified after synthesis, affecting their function, localization, and interactions.

Having understood these, we proceed into genomics and proteomics. This involves genome sequencing in sequencing entire genomes to understand the genetic blueprint of organisms. The Human Genome Project was a landmark study that mapped all the genes in human DNA. Having understood this, we proceed to the study on proteomics. This study means, we focus on the large-scale study of proteins, particularly their structures and functions. Techniques like mass spectrometry are used to analyse protein composition and interactions in cells.

Having done that, we can then proceed to understand molecular genetics. In this area we study gene editing and CRISPR.  (CRISPR means “clustered regularly interspaced short palindromic repeats”).  This is a technology that research scientists use to selectively modify the DNA of living organisms. CRISPR was adapted for use in the laboratory from naturally occurring genome editing systems found in bacteria.

They explore technologies like CRISPR-Cas9 that allow precise editing of DNA sequences. This has applications in gene therapy, agriculture, and synthetic biology.

We can then begin our study on epigenetics having finished studying the above. By this I mean studies on heritable changes in gene expression that do not involve changes to the DNA sequence. DNA methylation and histone modification are key mechanisms in epigenetics.

In medicine, an area I shall write separately later, molecular biology study cell that deals with signalling pathways, signal transduction and how they automatically commit suicide or apoptosis. Signal transduction investigates how cells respond to external signals through pathways involving receptors, second messengers, and kinases. Understanding these pathways is crucial for drug development, particularly in cancer therapy. The study of programmed cell death called apoptosis is a vital process in development and disease. Dysregulation of apoptosis is linked to cancer and neurodegenerative disorders.

Let us now list the biotechnology applications when we start learning molecular biology.

First, we learn about recombinant DNA technology like I also learn when I did my postgraduate in-service course. This involves manipulating DNA to produce genetically modified organisms (GMOs), therapeutic proteins, and vaccines. Insulin production through recombinant DNA technology is a notable example.

In their application in medicine, I shall write on this separately later, but briefly mention here, we apply molecular biology in molecular diagnostics.  The use of molecular techniques like PCR and next-generation sequencing (NGS) to diagnose diseases, including genetic disorders and infectious diseases is one of them. We also have gene therapy. In this area of medical specialty, we aim to treat or prevent diseases by correcting defective genes. Recent advancements in viral vectors and CRISPR have shown promise in treating genetic diseases like muscular dystrophy and sickle cell anaemia.

What about Recent Studies and Applications in Molecular Biology?

One of them among others is the CRISPR-Cas9 Advancements. A 2020 study demonstrated the potential of CRISPR-Cas9 for correcting mutations in the DMD gene, responsible for Duchenne muscular dystrophy. This research represents a significant step toward treating genetic disorders at the molecular level.

Then we also use our knowledge for the development of COVID-19 mRNA vaccines:

The development of mRNA vaccines, such as the Pfizer-BioNTech and Moderna vaccines, is a groundbreaking application of molecular biology, but has caused a global uproar about the use of these “suicidal vaccines.” I have received far too many adverse reports about mRNA vaccines from all kinds of people including from “famous” doctors, and of course from lay people.

 But unfortunately, almost none of the untold tens of hundreds of meetings and lectures on the Covid-19  given by international experts in various fields held at the prestigious Royal Society of Medicine in London where I was admitted as a Fellow in 1993, mentioned anything about the adverse effects of these mRNA vaccines.

These vaccines use synthetic mRNA to instruct cells to produce the spike protein of the SARS-CoV-2 virus, eliciting an immune response.

Our understanding of molecular biology also brings us into cancer immunotherapy. Recent advances in CAR-T cell therapy, a form of immunotherapy, have shown promising results in treating certain types of cancer. This approach involves genetically modifying a patient's T cells to target cancer cells more effectively.

Molecular biology is an incredibly dynamic and rapidly evolving field, with new discoveries continuously pushing the boundaries of what we know about life at the molecular level.  

I have only briefly outlined molecular biology above.  I shall write more later how we apply our knowledge on this in medicine.

But if my readers want more information in this area, below are some of the references they may read for themselves.

References for Further Reading

  1. Alberts, B., Johnson, A., Lewis, J., et al. (2014). Molecular Biology of the Cell (6th ed.). Garland Science.
    • A comprehensive textbook covering all aspects of molecular biology, from basic concepts to advanced topics.
  2. Lodish, H., Berk, A., Kaiser, C. A., et al. (2016). Molecular Cell Biology (8th ed.). W.H. Freeman and Company.
    • This textbook provides a detailed exploration of cellular processes and molecular biology techniques.
  3. Doudna, J. A., & Sternberg, S. H. (2017). A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. Houghton Mifflin Harcourt.
    • A book that discusses the discovery and implications of CRISPR technology.
  4. Recent Studies:

For up-to-date research articles, consider accessing journals like Nature Molecular Biology, Cell, and The Journal of Molecular Biology through databases like PubMed or ScienceDirect.

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