Overview

Description

CALENDAR DESCRIPTION:

An advanced treatment of specific topics related to the study of organic compounds. Topics which will be discussed will vary from one term to the next.

COURSE DETAILS:

1 tutorial hour/week - Monday, 1:30PM-2:20PM

Course description:  This modular survey course will introduce students to modern topics in chemical biology with an emphasis on applications of organic chemical principles to biological research and biotechnology.  The course is divided into three modules as follow:

The topics to be covered in the lectures will include synthetic and biosynthetic strategies used to produce derivatives of the major classes of biomolecules (nucleic acids, proteins, carbohydrates). Examples of chemical probes used in imaging, chemical genetics, and non-traditional methods for manipulating the levels and activities of biomolecules will be described. Examples of major experimental advances accomplished using these methods and tools will be described.  Emphasis will be placed on current and classic papers in the primary literature as well as critical review of recent research papers. Though not required, owing to the interdisciplinary nature of the subject matter of this course, students will benefit from an introductory-level understanding of biochemistry as well as cell and molecular biology.

COURSE-LEVEL EDUCATIONAL GOALS:

Literature discussions: The reading of scientific literature is an essential skill for scientists in all sectors; government, private, and academic. One aim of this course will be to improve skill at reading the literature through practice and discussion. Classes will therefore involve discussion of assigned literature including one paper per week. The articles will be circulated in class for the following week. Prior to class discussion prepare a concise write-up in which you answer the assigned questions. During class discussion we will briefly analyze the assigned paper and evaluate connections to the lecture material.

Topics covered in each course module:  

Module 1: Introduction to chemical biology – synthesis and biosynthesis of biomolecules 

1. What is chemical biology?
   • General structure of cells and cell theory
   • Introduction to cell cycle
   • Transient interactions enable biology
   • Revisiting the central dogma of molecular biology
2. Chemical biology of nucleic acids
   • Structure and properties of DNA and RNA
   • Revisiting replication and transcription
   • Roles of synthetic DNA in molecular biology
   • Introducing unnatural nucleobases into nucleic acids  
3. Chemical biology of proteins
   • Amino acids and proteins – structures and properties
   • Introduction to translation
   • Post-translational modifications
   • Methods to synthesize peptides and unnatural proteins  
4. Chemical biology of glycoconjugates
   • Structure and properties of glycoproteins and glycolipids
   • Biosynthesis of glycosidic linkages
   • Methods to globally manipulate glycans
   • Chemical synthesis of oligosaccharides  

Module 2 – High throughput and other enabling methods in chemical biology  

1. Developments in DNA sequencing
   • Dideoxy sequencing
   • Next and Third Generation sequencing methods
   • Select uses of DNA sequencing in directed evolution, biology, and DNA encoded libraries
   • Genome editing  
2. Strategies and concepts for molecular evolution
   • Introduction to combinatorial strategies to identify new molecular properties
   • Selections and screens
   • Directed evolution in vitro and in vivo
   • DNA templated libraries  
3. Chemical approaches to identifying targets and gene function
   • Forward and reverse chemical genetics – target based and phenotypic screening
   • Combinatorial libraries, DNA encoded libraries, Diversity Oriented Synthesis
   • Methods for target identification
   • Linking gene to gene function using chemical tools
   • Controlling proteins using small molecules  

Module 3 – Imaging life using chemical biology  

1. Introduction to detecting biomolecules in cells and in vivo
   • Basic principles of photophysics
   • Fluorescence and fluorescence imaging methods (FRAP, FLIP, FRET, FLIM)
   • Luminescence
   • Positron emission tomography  
2. Detecting biomolecules in cells using chemical biology
   • Proteins – genetically encoded fluorescent tags and small molecule labeling methods
   • Nucleic acids – genetically encoded tags and small molecule labeling methods
   • Glycans – metabolic engineering and small molecule labeling methods  
3. Detecting small molecules and enzyme activity in cells using chemical biology
   • Enzyme substrates, activity based proteomic probes, genetically encoded sensors
   • Improved fluorophores, quantum dots, nanoparticle quenching, luminescent molecules
   • Super resolution microscopy, STED, localization methods, and photoswitching
   • Small molecule sensors, photopharmacology

Grading

Materials

REQUIRED READING:

RECOMMENDED READING: