CORE CURRICULUM I

FALL SEMESTER

 
Module 1
Molecular Structure and Metabolism
(49 hours, Coordinator – J. Swaney)

This module serves to introduce students to fundamental concepts of molecular structure and function; these will serve as a basis for understanding both the biochemical basis for topics such as metabolism as well as aspects to be covered in other core modules, such as membrane transport phenomena and second messenger signaling.
 
Introduction and Fundamental Concepts (2 hrs) - J. Swaney
Water as a biological solvent, acid-base chemistry (pH, pK, Henderson-Hasselbalch equation), equilibrium (Gibbs free energy, coupled reactions, K), kinetics (activation energy, catalysts).
 
Macromolecules – Carbohydrates (1 hr) - P. Loll
Definition; classification as mono, di, and polysaccharides; isomers; redox reactions; linkage to proteins and lipids; proteoglycans and glycosaminoglycans. .
 
Macromolecules - Proteins (1.5 hrs) - B. Jameson
Structure (with forces that stabilize) and function of proteins: primary, secondary, tertiary, and quaternary structure (with emphasis on peptide bond formation and on protein folding); interaction of proteins with metals, lipids, sugars, and nucleic acids; denaturation/renaturation.
 
(Preceded by Self Study: Fundamental Concepts of Proteins, Amino acid general structure, classifications, abbreviations; acid-base properties of amino acids).
 
Hemoglobin Structure (1 hr) - B. Jameson
Discussion of how the oxygen-carrying ability of hemoglobin results from its primary, secondary, tertiary, and quaternary structures.
 
Enzymes (4 hrs) - M. Jorns
General properties, function as catalysts, types of catalysis (acid, base, covalent) using chymotrypsin as example, coenzymes, kinetics (Michaelis-Menton equation, Lineweaver-Burk plots Km and Vmax), inhibition (competitive and non-competitive), allosteric enzymes, regulation of enzyme activity, nomenclature.
 
Conference: Alcohol DH 1-data analysis (2 hrs) - M. Jorns
 
Protein Interactions (2 hrs) - I. Chaiken
Protein interactions and networks on and in cells; fundamentals of self-recognition and protein assembly; cooperative mechanisms of interaction; protein interactions and function in cell receptors and ribosomes; methods for measuring and characterizing protein interactions; antagonist design in drug discovery using HIV-1 envelope protein interaction machine case study.
 
Conference: Protein Folding (2 hrs) - P. Loll
Mechanisms by which chaperones and chaperonins promote protein aggregation and misfolding in cells. Articles covered:

• Xu, Z., Horwich, A. L., & Sigler, P. B. (1997) “The crystal structure of the asymmetric GroEL-GroES-(ADP)7 chaperonin complex” Nature 388: 741-750.
• Hartl, F. U. & Hayer-Hartl, M. (2002) “Molecular chaperones in the cytosol: From nascent chain to folded protein.” Science 295: 1852-1858.
• Tang, Y-C et al. (2006) "Structural features of the GroEL-GroES nano- cage required for rapid folding of encapsulated protein." Cell 125: 903-914.

Membranes (3 hrs) - J. Swaney
Membrane structure, transport across membranes (passive and facilitated diffusion and active transport), receptors and their role in signal transduction (adrenergic, insulin, and steroid hormone receptors).
 
Proteomics (2 hrs) - K. Vosseller
Sample preparation involving sub-cellular fractionation, affinity isolation of post-translationally modified peptides and protein complexes for analysis by mass spectrometry. Peptide chromatography coupled to mass spectrometry. Proteomic data acquisition and peptide sequencing/interpretation with automated search algorithms and manual inspection. Quantitative proteomics with differential isotopic labeling.
 
Purine & Pyrimidine Synthesis & Catabolism (2 hrs) - A. Mazin
Structure, nomenclature, and functions; de novo synthesis and salvage pathways, their regulation. Degradation of purines degradation of pyrimidines. The emphasis will be placed on the discussion of the biochemical mechanisms of the reactions involved in biosynthesis and its regulation.
 
Introduction to Metabolism & Glycolysis: Self Study
Anabolism and catabolism, basal metabolic rate, basic thermodynamics and thermodynamic coupling, high energy bonds, biological redox reactions, and intermediary metabolism (overview). Glycolysis as an example of an oxidative, catabolic pathway.
 
Acetyl CoA Generation & Utilization; Mitochondrial Electron Transport; Mechanisms of ATP Generation; Ion Transport (4.5 hrs) - I. Chaiken
Overview of catabolic pathways and central role of acetyl CoA in cellular formation of ATP energy source in cells; molecular organization, cellular localization, and regulation of enzyme systems that convert pyruvate to ATP; enzyme components, structural organization and regulation of the pyruvate dehydrogenase multienzyme complex that forms acetyl CoA from pyruvate; tricarboxylic acid cycle, its multienzyme molecular organization and reactions leading from acetyl CoA to respiration and phosphorylation; biological oxidation and reduction; mitochondrial electron transport (respiratory chain), its organization in membranes and the function of ETC protein complexes to reduce oxygen and drive and the formation of proton gradients in mitochondria ; the ATP synthase protein machine and its mechanism of function and regulation in the oxidative phosphorylation that leads to ATP.
 
Conference: Energy Metabolism (1.5 hrs) - I. Chaiken
Frontiers of research investigation of molecular mechanisms in the metabolic conversions of oxidative phosphorylation; diseases associated with the mitochondrial enzyme systems of oxidative phosphorylation and production of ATP; interrelationship of mitochondrial redox proteins, membranes and apoptosis.
 
Glycogen Metabolism; Regulation of Glycolysis; Gluconeogensis; Pentose Pathway (4.0 hrs) - P. Loll
Structure and function of glycogen, storage sites, pathways of synthesis and degradation, regulation of the pathways by covalent modification and allosteric effectors. Cellular uptake and utilization of glucose, regulation of glycolysis (with emphasis on gluco/hexokinase, phosphofructokinase, pyruvate kinase); metabolism of fructose and galactose; pentose phosphate pathway; gluconeogenesis reactions, regulation, compartmentalization.
 
Fatty Acid Synthesis; Fatty Acid Oxidation; Ketones (2.5 hrs) - B. Jameson
Significance and overview, fatty acid synthesis, modification of endogenous and dietary fatty acids, fatty acid oxidation; ketogenesis, peroxisomal degradation.

Amino Acid Derived Hormones (1.5 hrs) - J. Swaney
Synthesis and function of regulators derived from a single amino acid with emphasis on the catecholamines and melanin from tyr, serotonin and melatonin from trp, histamine from his, and GABA from glu; degradation of these regulators; synthesis, function and inactivation of NO.
 
Amino Acid Metabolism (1.5 hrs) - K. Vosseller
Overview of amino acid metabolism with emphasis on amino acid pool, nitrogen catabolism, urea cycle, use of alpha-keto acid skeletons in energy metabolism (gluco- and ketogenic amino acids), metabolism of branched - chain amino acids with emphasis on the production and roles of gln and ala.
 
Review & Integration of Energy Metabolism (3.5 hrs) - D. Ferrier
A refocus on the “big picture”; role of liver, muscle, adipose and brain in the fed and short-term fasted states; review (overview) of the key pathways of the fed and fasted states with emphasis on regulation; tissue interrelationships; key molecules; adaptation to long-term fasting with a focus on tissue inter-relationships; aerobic-anaerobic transitions; resting muscle-contracting muscle transitions.
 
Lipids, Triglycerides, Eicosanoids, Cholesterol Metabolism (4 hrs) - J. Swaney
Glycerol- and sphingosine-based polar lipids with emphasis on TG, PL and sphingoglycolipid synthesis; eicosanoid metabolism and biological activities (emphasis on PGI2, TXA2, LTC4); cholesterol synthesis and regulation; overview of digestion. Function, classification, structure, and function of lipoproteins.

Conference: Steroid synthesis (3 hrs) - J. Swaney
Team-learning exercise to practice critical reading of the literature: Brown and Goldstein (Nobel Laureates), “Multivalent Control of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase”, J. Biological Chemistry, 263, pp. 8929-8937, 1988.

Module 2
Molecular Biology and Genetics
(36 hours, Coordinator – R. Rest)

The goal of the molecular biology module is to understand the basic concepts of prokaryotic and eukaryotic DNA replication, transcription and translation, and their regulation. This module will also familiarize students with the underlying mechanism regulating the inheritance of genetic material. In addition, students will be introduced to genetic methodologies used to manipulate, interpret and define gene function. The information learned in this module will be the basis for understanding many of the basic concepts in cell biology presented later in the course, and later in your career.
 
Nucleic Acid Structure & Analysis (2 hrs) - T. Edlind
Covers the basics of DNA and RNA structure and its relevance to both cellular function and to widely used molecular biology methods.
 
Recombinant DNA I (2 hrs) - T. Edlind
Covers the basics behind specific methods, including nucleic acid purification, hybridization, sequencing, sequence analysis, gene expression analysis, and PCR.
 
Recombinant DNA II (2 hrs) - M. Jorns
The lecture will focus on DNA cloning (including creation and screening of DNA libraries), expression of recombinant proteins and site-directed mutagenesis (including selection of target sites, design principles).
 
DNA Replication (2 hrs) - E. Noguchi
Provides an overview of DNA replication and discusses semiconservative replication, replication forks, origin of replication, semidiscontinuous synthesis, primers, proof-reading, proteins of DNA replication, the replication of a bacterial chromosome and a detailed look at elongation and initiation of DNA replication, the replication of a eukaryotic chromosome including the replication of the ends of linear eukaryotic chromosomes.

DNA Mutation and Repair (2 hrs) - A. Mazin
DNA damage results both from internal and external assaults on the cell. During the normal process of DNA replication, polymerase errors not corrected lead to permanent changes in the nucleotide sequence that can have dire consequences on cell viability. We are exposed every day to environmental factors such as alkylating agents, toxic hydrocarbons and pesticides, which target and modify DNA in harmful ways. The goal of this lecture is to provide an overview of the types of damage to DNA, their causes, and the cell pathways that sense and repair this damage.
 
Prokaryotic transcription I (2 hrs) - R. Rest
Covers the basics of RNA structure and transcription in prokaryotic cells and discusses the elements of bacterial promoters, the structure and function of bacterial RNA polymerase, processivity and transcription termination.
 
Prokaryotic transcription II (2 hrs) - R. Rest
Focuses on the regulation of transcription in prokaryotic cells and discusses the binding of transcription regulators to DNA, the characteristics and function of DNA binding proteins, the role of different sigma factors, negative and positive regulation, two component regulatory systems and global gene regulation in bacteria.
 
Eukaryotic transcription I & II (4 hrs) - J. Clifford
This lecture will focus on transcription in eukaryotic cells and discuss the basic transcription unit including promoters, terminators, up- and downstream regulatory sequences, transcription factors, cis and trans elements, as well as inhibitors of transcription and post-transcriptional modifications to RNA.
 
RNA processing I (2 hrs) - G. Johannes
Focuses on the processing of RNA in eukaryotic cells with a discussion of the types and structure of RNA, the processing of rRNA, tRNA, and mRNA, RNA transport, RNA stability and RNA interference.
 
RNA processing/Translation (2 hrs) - M. Bouchard
Provides an overview of protein synthesis with a discussion of the genetic code, the mechanism of protein synthesis, a comparison of the key features of prokaryotic and eukaryotic translation machinery, and the regulation and inhibition of protein synthesis.
 
Translation (2 hrs) - A. Vaidya
This lecture deals with regulatory aspects of translation. Translational block of maternal mRNA and the underlying molecular mechanisms are discussed. Subcellular localization of mRNAs destined for different parts of the cell is discussed using examples in the yeast and neurons.
 
Bioinformatics (2 hrs) - B. Jameson
This lecture provides a description and discussion of relational databases, the differing algorithms for sequence alignments and the use of various sequence search programs, such as BLAST and FASTA.
 
Genomics I and II (4 hrs) - B. Bergman
These lectures will explore the analysis of complete genome sequences and use of the information for whole genome expression analysis and genetic analysis. The lectures will utilize studies from recently completed genomes and genomic studies to illustrate how to sequence a genome, approaches to gene prediction, and the types and use of microarrays for whole genome expression analysis.
 
Mitosis/Meiosis/Recombination (2 hrs) - A. Mazin
In this lecture, we will discuss chromosome pairing, synaptonemal complex formation and genetic recombination during meiosis, and the coordination of these processes with meiotic cell cycle progression. Specifically, we will focus on the interhomolog interactions that occur during meiotic prophase and are necessary for reductional chromosome segregation at the first meiotic division. Important events include homologous chromosome pairing, assembly of the synaptonemal complex, genetic recombination, and the formation of chiasmata.
 
Gene Inheritance and Mapping (2 hrs) - L. Blankenhorn
Genetic maps allow a connection to be made between structure and function: gene-> protein -> function. This lecture will provide an overview of genetic maps and compare and contrast the different kinds of maps. The basic methods of mapping, the analysis of patterns of inheritance, and the application of genetic mapping to understanding genetic defects associated with disease will be discussed.
 
Transgenic Applications (2 hrs) - M. Bouchard
Focuses on model transgenic organisms in research and discusses the generation, use and analysis of transgenic plants (Agrobacterium) , transgenic worms (C. elegans), transgenic insects (Drosophila), and transgenic mice as well as gene targeting strategies to construct ‘knockout’ and ‘knockin’ organisms.

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