This was the title of a talk by Dr Zoë Waller of the University College London School of Pharmacy, where she leads a team researching DNA.
Zoë gave an introduction to DNA. Our bodies have many different types of cells and inside the cell is a nucleus. Within the nucleus are chromosomes, which are made up of DNA. DNA is made from 4 ‘bases’ which are in pairs, in shorthand G is always paired with C and A paired with T. The ‘genetic code’ that defines the nature of the cell and therefore our complete bodies is the sequence of the bases.
For humans the sequence of bases is 3 billion long, much longer than a worm’s 97 million but much less than a newt at 18.6 billion. The longest currently known are in plants, in particular 148 billion for japonica.
DNA provides the code or blueprint for a human. From DNA a working copy called RNA is used to make a protein, for instance insulin. DNA is inherited, so many traits are inherited from our parents.
DNA’s structure is a double helix, like a twisted ladder. The links between the two helixes are the base pairs, so G and C, or A and T. This structure was first proposed by Watson and Crick in 1953, although DNA had been known from the 1800s. In 1962 it was found that if you had long sequences of the base G it could form gels and square structures, and in 1993 that long base C sequences can form knotted structures.
Zoë has a YouTube channel and you can find a presentation on “The Changing Shape of DNA” as described above at: https://youtu.be/7rzcYl55GYQ
In 2003 it was discovered that only 2% of the DNA sequence encodes proteins. 43% can fold into different structures such as a special DNA quadruple helix structure. So, what do these shapes do?
What is known is that the insulin gene has a special region where the DNA can fold into unusual structures. These structures affect how much insulin is made and therefore the development of diabetes. Zoë’s team is looking for compounds that will prompt changes in the DNA structure and will therefore act as switching compounds, turning on or off the production of insulin. Cells grown in petri dishes are given glucose and will make insulin, and different compounds have been found to increase or decrease that insulin production.
This research is aimed at improving the compounds to use as tools to understand insulin production and diabetes better. Specifically, work is focused on improving and understanding what the compounds actually do, what proteins bind the special structures in the polymorphic region, and how does genetic mutation and epigenetic modification affect the structures. This will hopefully lead to potential treatments for diabetes, chemical tools to understand better how diabetes develops, and being able to predict who might get diabetes.
Since giving the talk Zoë has kindly sent some references for those who would like to explore the topic further:
Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? (nih.gov)
The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure (nih.gov)
And some articles which are aimed at a general audience:
‘Quadruple helix’ DNA seen in human cells – BBC News
DNA i-motifs found in human cells (acs.org)
New form of DNA discovered inside living human cells | The Independent