53BP1 the magnificent tumour suppressor

Introduction

Summary in 4 parts

Part 1 - The absence of p53

When absent p53 is mutated or absent in more than 50% of all cancers. His absence makes the cells unable to correctly respond to stress stimuli (usually affecting the DNA, p53 is often call ’the guardian of the genome') what usually results in uncontrolled cell proliferation.

Part 2 - The absence of 53BP1

53BP1 is a factor critical in DNA doublestand break (DSB) repair and therefore its abnormal function results in toxicrepair. However, one of the major physiological processes where 53BP1 isessential is in the generation of the antibody repertoire. The absence of 53BP1therefore results in deficient immune responses to infections as the immunecells are unable to generate specific antibodies to recognise pathogens.Regarding its contribution to p53 responses (which is the major focus of mystudy), 53BP1 promotes complete p53 action, although I am afraid that we stilldon’t know the physiological relevance of this at an organism level. Perhaps,alterations in 53bp1-p53 regulation may also lead to abnormal cellproliferation.

Part 3 - The absence of BRCA1

BRCA1 and 53BP1 act in DSB repair keeping an equilibrium tightly regulates during the cell cycle. In the absence of BRCA1, 53BP1 carries out all the DSB repair which results in a higher frequency of errors in DNA repair. BRCA1 deficiency is strongly associated with breast and ovarian cancer, and mutations in the BRCA1 gene can be inherited generating a higher predisposition to suffer those types of cancers.

Part 4 - Normal scenario

When those proteins act correctly, the stress stimuli are detected by the cells and p53 decides the cell fate, either the cell can deal with the stress and stayalive, or the damage is too much, and the cell must die. 53BP1 and BRCA1 cope with DNA breaks generated due to exposure to radiation or other DNA damaging agents we can be exposed to and promote accurate and reliable repair that allowour cells to grow normally and perform its function within a tissue or organ.Those three proteins are called tumour suppressors, as when they act correctly, they are constantly protecting our cells from becoming tumorigenic.

Artwork

The challenge in this project was to explain the action of p53 in the 4 scenarios? My first request of Raquel Cuella-Martin was to break down the complex science in to a simple narrative which I could then translate into a visual form. Raquel needed the science translated in to a story that she could tell when in front of a public audience for her outreach work. She needed me to create a range of artwork that told the story visually in multiple formats including a large printed (from a digital file) illustrated diagram. Illustrated slides for PowerPoint resources that she could use for presentations at public engagement and events. By the end I even designed t-shirts that she wore at events to engage her audience (especially in schools). The Digital illustration to this day hangs on the wall in the genetics department corridor next to the lab where she worked.

The characters

I first came up with the idea of drawing a range of metaphorical cartoon characters that explained the relationship and action of p53 in the real-world context. So I first visualised all the characters who populated the 4 scenarios. Then I used the characters to create scenes where the actors were demonstrating the 4 scenarios.

Final artwork

The final artwork shows all the 4 scenarios in relation to p53. The artwork is split in to 2 sides. Side one shows what happens when p53 is working correctly. Side 2 shows when p53 is absent and the negative consequences of that!