Chemical Biology & Molecular Interactions - CHE00019M

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  • Department: Chemistry
  • Module co-ordinator: Prof. Gideon Davies
  • Credit value: 10 credits
  • Credit level: M
  • Academic year of delivery: 2019-20

Module summary

A module that first introduces the techniques used in academia and industry to study the interactions of small molecules such as drugs with target proteins and then unveils the emerging field of chemical biology - the use of small molecules to study cellular biology. This is a key area where chemists are now able to make biological breakthroughs leading to new insights and new medicines.

Module will run

Occurrence Teaching cycle
A Autumn Term 2019-20

Module aims

This module will survey contemporary research in the area of Chemical Biology – using chemical methods to ask questions about biological systems.

Module learning outcomes

  • Students will 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.  They will learn about key concepts in Chemical and Synthetic Biology such as chemical genetics, bioorthogonal chemistry, activity-based protein profiling, reprogramming the genetic code and genome editing.
  • Students will 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 learn about molecular biophysics methods which can be employed to probe intermolecular interactions. This will span both fundamental studies of the kinetics and thermodynamics of protein-ligand interactions and investigations of individual molecules within the cell.
  • Students will learn about a range of experimental methods, such as NOESY, HSQC, surface plasmon resonance, ITC, FRET etc, and will learn to evaluate these methods to decide which is most appropriate to solve a particular problem.

Module content

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.

REHu

4 lectures

 

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.

REHu

3 lectures

 

1×3 h workshop

Chemical Biology.

Use of TAFT, Hammett plots and kinetic isotope effects to study enzyme action and inspire the design of enzyme inhibitors. The concept of using rationally-designed inhibitors in living systems – Chemical Genetics -will be introduced. The concept of bio-orthogonal chemistry in living systems. Martin Fascione will introduce the reaction mechanisms of different bioorthogonal reactions. Feeding cells modified compounds for subsequent reaction. In vivo copper-free click chemistry using strained alkynes. Finding kinase/target pairs. Activity-based protein profiling and the use of bump-and-hole. An introduction to the new area of synthetic biology in which cells are redesigned to accommodate non-natural amino-acids and bio-orthogonal chemistries.

GJD/MAF

9 lectures

 

Workshops:

Workshop – learning how to look at protein structure and further discussion of methods for probing interactions (3hrs, not assessed, but examinable) - REHu

Workshop introducing the assessment where each student is given a protein(s) and some papers from which they generate a short summary of an area of chemical biology research (3hr workshop; 12 hours private study required) – REHu

Assessment

Task Length % of module mark
Essay/coursework
Assessed Workshop
N/A 30
University - closed examination
Chemical Biology & Molecular Interactions
1.5 hours 70

Special assessment rules

None

Additional assessment information

By 1½ h written examination paper (70%) and by continuous assessment (written report on a subject studies using computer graphics with wider reading; 30%). The deadline for handing in work is 2 weeks after the assessed workshop.

Reassessment

Task Length % of module mark
University - closed examination
Chemical Biology & Molecular Interactions
1.5 hours 70

Module feedback

The closed examinations are marked typically within 10 days with mark slips (with per-question break-down) being returned to students via supervisors. Outline answers are made available via the Chemistry web pages when the students receive their marks, so that they can assess their own detailed progress/achievement. The examiners reports for each question are made available to the students via the Chemistry web pages.

Indicative reading

This is a research-led course so up to date scientific publications will form the majority of the reading. Approximately two original papers / reviews per lecture. The "continuous assessment" following the workshop will also require extensive reading.



The information on this page is indicative of the module that is currently on offer. The University is constantly exploring ways to enhance and improve its degree programmes and therefore reserves the right to make variations to the content and method of delivery of modules, and to discontinue modules, if such action is reasonably considered to be necessary by the University. Where appropriate, the University will notify and consult with affected students in advance about any changes that are required in line with the University's policy on the Approval of Modifications to Existing Taught Programmes of Study.