Chemical & Synthetic Biology - CHE00037M

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  • Department: Chemistry
  • Credit value: 10 credits
  • Credit level: M
  • Academic year of delivery: 2022-23

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. We will also look at synthetic biology - reprogramming nature to devise new biological species.

Module will run

Occurrence Teaching period
A Spring Term 2022-23 to Summer Term 2022-23

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 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 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. Including metabolic labelling - where unusual chemical species may be introduced into living systems.
  • Students will learn in depth organic reaction mechanisms
  • Students will learn about directed evolution techniques to modify the function of biological molecules and systems,

Module content

Chemical and Synthetic Biology.

Physical Organic Chemistry: Use of TAFT, Hammett plots and kinetic isotope effects to study enzyme action and inspire the design of enzyme inhibitors (GJD 1 & 2). The concept of using rationally-designed inhibitors in living systems – Chemical Genetics - will be introduced (GJD 3). The concept of bio-orthogonal chemistry in living systems, in vivo copper-free click chemistry using strained alkynes (GJD 4). Activity-based protein profiling (GJD 5) and the use of bump-and-hole strategies to define kinase/target pairs (GJD 6). And 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 7).

Building upon these lectures, we will expand upon the organic reaction mechanisms of different bioorthogonal reactions (MAF 1). This will lead into genome editing (MAF 2), followed by the use of targeted protein degradation using bifunctional small molecules (PROTACs) with the study of the ubiquitin modification as an example (LIW 1). Then we will discuss the use of metabolic labelling - feeding cells with modified carbohydrates and lipids for cellular studies of these biomolecules (LIW 2 & 3) .


The course will finish with 4 lectures on evolving biomolecules for new function. This will begin with the principles of directed evolution (CDS 1) followed by the design and use of artificial enzymes (CDS 2). Phage display and related techniques will be introduced for the identification of binding sequences (CDS 3), along with chemical strategies to improve evolution and move past the limitations of natural amino acids and primary peptide sequences (CDS4).

There will be a 1 x 3h graphics workshop – X-ray structures - learning how to look at protein structure and protein-ligand interactions (not assessed, but examinable)

GJD (7 lectures)

MAF (2 lectures)

LIW (3 lectures)

CDS (4 lectures)

JA (1 workshop)

The final workshop will cover the selection of topics / papers / coordinate files for the assessed workshop.

JA

1×3h workshop preparation for assessment

Indicative assessment

Task % of module mark
Essay/coursework 30
Online Exam -less than 24hrs (Centrally scheduled) 70

Special assessment rules

None

Additional assessment information

The online exam (based on a 1.5-hour paper delivered over 4.25 hours) has two compulsory 20-mark questions.

The second workshop is assessed through a project report of 4-5 pages based around a specific paper (and wider related reading) and analysis of the structure(s) on computer graphics. 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; approx. 12-20 hours private study required). The deadline for handing in work is 2 weeks after the assessed workshop.

Indicative reassessment

Task % of module mark
Essay/coursework 30
Online Exam -less than 24hrs (Centrally scheduled) 70

Module feedback

Exam results with per-question breakdown are returned to the students via supervisors within 5 weeks (as per special approval by the University Teaching Committee). 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.

For the continuous assessment, the students receive an annotated mark sheet, with each of the individual sections commented upon individually. Marks are awarded for: Quality of introduction (20%); Quality of images (15%); Relevance of images (15%); Description of what the images show (15%); Summary of experimental strategy including (as appropriate) chemical synthesis, molecular interaction techniques, thermodynamics (35%)

Indicative reading

This is a research-led course so up to date scientific publications will form the majority of the reading