Chemical Biology and Molecular Interactions

Chemical biology is the use of chemical methods and tools to investigate biological systems. This module begins with an introduction to cellular processes and some of the current topics and questions in chemical biology.  There is then a survey of the modern biophysical methods that are used to interrogate biomolecules and their interactions, in particular with small chemical molecules.  

This is illustrated with recent examples of how chemical tools have generated fundamental understanding of cellular processes and how they may be manipulated, in particular to investigate the molecular mechanisms of disease.  The module concludes with some examples of the cutting edge techniques and research ideas in this area.  

Learning objectives

  • Understand the basic principles of the biophysical methods (X-ray crystallography, NMR spectroscopy, Surface Plasmon Resonance, Isothermal Titration Calorimetry), appreciate the opportunities and limitations of their use and how to interpret the experimental results
  • Gain an insight into how chemistry can be taken into the cell – in particular considering reactions using bio-orthogonal reagents which are compatible with living systems. 
  • Gain an insight into the physical organic chemistry of enzymes, and learn how core chemistry methods such as Hammett plots and kinetic isotope effects can be applied in a biological setting.
  • Students will have the background knowledge and experience to understand and assess new research in the area of chemical biology, for example being able to understand, summarise and critique new research papers in the area

Current topics in molecular and cell biology

These overview lectures will introduce biological processes and systems, such as the cell cycle (kinases and cyclins), signal transduction pathways (kinases / phosphatases), DNA transactions (gene regulation / transcription factors) and metabolism. We will use the example of cancer biology to illustrate how these processes can be probed to understand the molecular basis of the condition. This will provide the necessary context to understand how chemical methods have had impact on these areas of biology, where modern research is uncovering remarkable details of how complex organisms function and are regulated.          

Modern methods of probing biological interactions 

Recent advances in instrumentation and methods have opened up considerable opportunities to identify and characterise interactions between biological molecules, substrates and inhibitors. These lectures will reinforce and extend earlier lecture courses to discuss the experimental techniques (and their physical basis). This will include Isothermal Titration Calorimetry, Surface Plasmon Resonance, X-ray crystallography, thermal shift and the multitude of NMR experiments (e.g.HSQC, X-filtered NOESY, STD, LOGSY) that allow the details of interactions between molecules to be probed.

Chemical Biology 

These lectures will explain some of the contemporary chemical biology methods and approaches.  Examples will include: (1) the use of TAFT, Hammett plots and kinetic isotope effects to study enzyme action and inspire the design of enzyme inhibitors; (2) the concept of using rationally-designed inhibitors in living systems – Chemical Genetics; (3) the reaction mechanisms of different bioorthogonal reactions for labelling biological molecules, such as In vivo copper-free click chemistry using strained alkynes; (4) Activity-basedare redesigned to accommodate non-natural amino-acids and biorthogonal chemistries; (6) gene-editing – the most recent advance for engineering biology. 

Prerequisites

Chemistry Core Modules 1- 4