Medical Biology and Genetics Lecture 1 PDF

Medical Biology and Genetics for Pharmacy 2020-2021 Lecture 1: Macromolecules, biosynthesis and model organisms Assist. Prof. Berrak ÇAĞLAYAN [email protected] Reference Book: Essential Cell Biology  Outline of MBG Course Lecture 1: Macromolecules, biosynthesis and...

Medical Biology and Genetics for Pharmacy 2020-2021 Lecture 1: Macromolecules, biosynthesis and model organisms Assist. Prof. Berrak ÇAĞLAYAN [email protected] Reference Book: Essential Cell Biology  Outline of MBG Course Lecture 1: Macromolecules, biosynthesis and model organisms Lecture 2: Cellular structure and organelles Lecture 3: DNA, chromosomes and genome Lecture 4: DNA replication and repair mechanisms Lecture 5: RNA and protein synthesis Lecture 6: Control of gene expression Lecture 7: Epigenetics and epigenome Midterm Exam Lecture 8: Cell junctions and signal transduction Lecture 9: Cell cycle and cell division Lecture 10: Cellular aging and cell death Lecture 11: Cancer and molecular mechanisms Lecture 12: Stem cell biology and treatments Lecture 13: Mendelian and non-Mendelian genetics Lecture 14: Genetic disorders Final Exam  Learning Objectives ✓ To describe the hierarchical organization of life ✓ To describe atoms and atomic bonds ✓ To compare the ways in which electrons can be donated or shared between atoms ✓ To explain the importance of enzymes in biosynthesis ✓ To explain dehydration (condensation) and hydrolysis reactions ✓ To discuss and explain the roles of carbohydrates, fatty acids, proteins and nucleic acids in cells ✓ To understand and compare the use of animal models to study human life Hierarchical organization of life Cells are made of relatively few types of atoms Covalent bonds are much stronger and more stable than noncovalent bonds Ionic bonds form by the gain or loss of electrons A large molecule, such as a protein, can bind to another protein through complementary charges on the surface of each molecule. When present in large numbers, weak noncovalent bonds on the surfaces of large molecules can promote strong and specific binding. Cells contain four major families of small organic (carbon-containing) molecules Each macromolecule is a polymer formed from small molecules called monomers or subunits. Subunits are linked together by covalent bonds. On the basis of weight, macromolecules are more abundant in cells. Small molecules and ions make up of only ~7% of the cell mass. Macromolecules are formed by adding subunits to one end In a condensation reaction; a bond is formed between an –OH group on one sugar and an –OH group of another and water is expelled. Sugars provide an energy source for cells and are the subunits of polysaccharides Note that structural formula can be represented in several ways. Small oligosaccharide + protein = glycoprotein Small oligosaccharide + lipid = glycolipid Glycoproteins and glycolipids are found on cell surface and help cells attach to one another and form blood types in humans. Amino acids have: an amino group, a carboxyl group and a side chain (R) attached to their α-carbon atom. Amino acids are the subunits of proteins Amino acids in a protein are held together by peptide bonds Chemical structure of Adenosine TriPhosphate (ATP) A fatty acid is composed of a hydrophobic hydrocarbon tail attached to a hydrophilic carboxyl group The most important function of fatty acids in cells is in the construction of cell membranes Most proteins and many RNA molecules fold into only one stable conformation. Non-covalent bonds specify the precise shape of a macromolecule and its binding to other molecules. Non-covalent bonds mediate interactions between macromolecules Both covalent and non-covalent bonds are needed to form a macromolecular assembly  Enzymes and Enzymatic Reactions Cells obtain energy by the oxidation of organic molecules Cells use enzymes to catalyze the oxidation of organic molecules in small steps, through a sequence of reactions that allows energy to be harvested in useful form. Enzymes organize the cell metabolism Enzymes - accelarate or catalyze specific reactions - are highly selective - can bind to one or more substrates - have a catalytic site - lower the activation energy of reactions - end with “-ase” Enzymes reduce the energy needed to initiate spontaneous reactions Enzymes convert substrates to product while remaining unchanged themselves Molecules are in constant motion in the cell (Diffusion) Reaction coupling is used to drive energetically unfavorable reactions Activated carriers can store and transfer energy in a form that a cell can use Experimental Organisms vs Model Organisms Model organisms are non-human species that are extensively studied in order to understand biological mechanisms that are also conserved in humans. Frog has been used as a model organism since late 1600s to study circulation, muscle contraction and respiration! Model organisms are used to understand the fundamental mechanisms of life - Some organisms are more appropriate than others for understanding certain biological processes. - To study a biological process, evolutionary conservation of genes, proteins, organelles or cell types are considered. - Simplicity vs complex cellular organization?? The bacterium Escherichia Coli (E. coli) is an ideal model organism with certain advantages - Small, rod-shaped bacterium with simple genome - Normally lives in the gut of humans and other vertebrates, but can be easily produced in the lab Ideal for - Bacterial gene control and protein function studies - Cell cycle and bacterial metabolism - New antibiotic production The single-celled yeast Saccharomyces cerevisiae is a model eukaryote - S.cerevisiae is a single-celled organism with the cellular organization of a eukaryote. (=nucleus + organelles) - Easily grown and genetically manipulated Ideal for - Control of cell cycle and cell division - Aging - Protein secretion - Chromosome structure Arabidopsis thaliana has been chosen as a model plant - A flowering plant - Can be grown indoors in large numbers - Because genes found in Arabidopsis have counterparts in agricultural species, studying this simple weed provides insights into the development and physiology of the crop plants - Give insights into the evolution of all the other plant species that dominate nearly every ecosystem on Earth Fruit fly Drosophila melanogaster is a valuable model for embryonic development Many of the core developmental systems are evolutionarily conserved - Whole genome information and many mutant lines are available. Ideal for - Development of the body plan - Formation of the nervous system, heart and musculature - Control of cell polarization - Effects of drugs or pesticides Roundworm Caenorhabditis elegans is a well-suited model for genetic studies - Has exactly 959 cells in an adult body. - Strict and predictable rules determine the fate of each cell. Ideal for - Cell lineage studies - Formation and function of the nervous system - Development of the body plan Zebrafish Danio rerio are popular models for studies of vertebrate development - Its genome can be easily manipulated; several mutants were formed. -It is transparent for the first two weeks of its life. Ideal for - Cell lineage studies - Formation and function of the nervous system - Development of the body plan Xenopus laevis is ideal for developmental studies due to ex-utero egg growth - Their eggs are big and easy to manipulate. - Large-celled embryos develop outside the mother. Ideal for - Developmental biology - Egg fertilization and embryogenesis - Cell fate tracking House mouse Mus musculus is the predominant mammalian model organism - Humans and mice have similar genes and similar development. - Small size makes it easier to produce several in small spaces. Ideal for - Cancer studies - Human disease models - Immune response to diseases Many genes which control the developmental processes are similar in humans and other animals Not all genes or proteins are evolutionarily conserved. But, developmental genes are remarkably conserved during evolution, meaning that their functions are similar in humans and in other species. Next Class Next lecture: Cellular structure and organelles