DNA-lab “Healthy or ill: Just a single wrong fold”

This lab shows how the folding of proteins is affected by a small distortion of its structure. A minor change with major consequences....

Our DNA contains the encoded information for making proteins; the complex molecules that are responsible for many processes in the cell. Changes (mutations) in a certain gene will lead to changes in the relevant protein and that can result in disease.

Folding

To function properly, a protein has to fold itself in a very specific manner. Mutations can distort this folding process, leading to wrongly folded proteins. Diseases such as diabetes, cystic fibrosis or Alzheimer’s disease are caused by such wrongly folded proteins.

Techniques

In this DNA-lab, the students will search for the molecular cause of several diseases associated with wrongly folded proteins. They are introduced to techniques to track ‘healthy’ and ‘diseased’ proteins in cells and they will apply elementary techniques used to determine protein structures (comparable to X-ray diffraction). Finally, they will perform an experiment, which demonstrates that distortion of the protein structure leads a loss of protein activity.

Context

This practical covers a number of molecular biology topics related to the origin of diseases. The students will examine topics such as heredity, proteins and DNA and connect these to the question of why some people are born ill whereas others develop diseases later in life. They are also introduced to fundamental biochemical aspects of protein folding. Social implications of genetic biomedical research are specifically discussed in this DNA-lab.

Required knowledge

It is advisable that the students are familiar with certain concepts beforehand:

Biology
• The student should be familiar with the localisation of the DNA in a cell. Organelles such as the cell nucleus and the cytoplasm should have already been discussed in class.
• The student should know about the subcellular structure of a eukaryotic cell; nucleus, cytoskeleton and the main features of the organelles involved in protein synthesis.

Molecular biology and molecular chemistry
• The student should be familiar with the mutual connection between DNA, RNA and proteins.
• The student can explain that specific genes code for specific proteins.
• The student can explain that a protein is made up of amino acids and that proteins can have enzymatic and structural functions.
• The student is familiar with the chemical formulas of amino acids and proteins.
• The student knows that functional proteins are specifically folded in a three dimensional structure.
• The student has elementary knowledge on heredity and is familiar with concepts such as allele, gene, DNA and chromosomes.

Applications of this DNA-lab

• Understanding the relationship between structural folding of proteins and their function in relation to disease.
• Basic insights into the consequences and causes of protein folding at a chemical level.

This DNA-lab can be used in both biology and chemistry lessons.