Basic molecular biology in biomedical research

Milestones of molecular biology

The major advances in genetic engineering have occured during the last 6 decades, but the history of molecular biology started at the end of the XIX century with the research of Darwin and Mendel. On his book "On The Origin of Species", Charles Darwin explained that heredity is the mechanism that perpetuates variations, since the traits in offspring result from a blending of the traits of each parent. The Austrian friar Gregor Mendel conceived the idea of heredity units, which he called "factors" (later known as "genes"), by studying Pisum sativum, or the common pea plant. Mendel proposed that "factors" normally occur in pairs and these two "particles" of the factors (later known as "alleles") segregate from each other in the formation of gametes. Therefore, Mendel stated that each individual inherits two "particles" for each trait, one from each parent.  In 1869, Friedrich Miescher first isolated what he called "nuclein" (later known as "deoxyribonucleic acid" or "DNA" inside the nuclei of human white blood cells. 

 

In 1953, Dr. James Watson and Dr. Francis Crick deduced the three dimensional, double-helical model for the structure of DNA, based on some crucially important X-ray chrystallography work of Dr. Rosalind Franklin and Dr. Maurice Wilkins. Watson, Crick and Wilkins received the Nobel Prize in Medicine for the double-helix model of DNA in 1962, but the scientific work of Rosalind Franklin was not recognized. The picture on the right pannel illustrates the schematic respresentation of the double-helix model of DNA proposed by Watson and Crick and published in the prestigious Nature journal (view the manuscript here).

In 1990 the second major milestone in the genetics of the XX century started with the sequentiation of the human genome in the "Human Genome Project", that concluded in 2003. A working draft of the Human Genome was completed and simultaneously published in Nature and Science on February 15, 2001.

New challenge in molecular biology: the ENCODE project

ENCODE (acronym of ENCyclopedia Of DNA Elemens) is a project funded by the National Human Genome Research Institute to identify all regions of transcription, transcription factor association, chromatin structure and histone modification in the human genome sequence. Thanks to the identification of these elements, 80% of the components of the human genome now have at least one biochemical function associated with them, in particular, the non-encoding regions. In this link to the ENCODE project, the most relevant results obtained in relation to the organization and regulation of the genes are shown.

The identification of new elements of the human genome has revealed new insights into biomedical research, as you can see in this video:

The central dogma of molecular biology consists of three main processes: DNA replication, RNA transcription and protein translation. Some of the basic techniques used in biomedical research are shown below:

Molecular techniques for the study of DNA:

• Analysis of numeric chromosomal anomalies: cariotype.
• Analysis of structural chromosomal anomalies: FISH 
• Detection of mutations: RFLP.
• Study of gene function: transgenic animals.

Molecular techniques for the study of RNA:

• Conversion of RNA to cDNA: reverse transcription.
• Gene expression analysis: conventional PCR, real-time PCR and microarrays.

Molecular techniques for the study of proteins:

• Quantification of proteins: ELISA, western-blot and proteomics.
• Localization of proteins: immunohistochemistry.
•  Study of protein function: stimulation of cell cultures, inoculation in experimental animals or patients.