Team:Stockholm/Project Idea/Introduction

Introduction

Many different ideas were discussed during the startup of our iGEM project. We finally decided to focus on the skin disorder Vitiligo. We have discussed our project idea with two leading Vitiligo researchers in Sweden (Mats J. Olsson & Håkan Hedstrand, Uppsala University), both who have shown interest and encouraged us to go ahead with the project. We have also been given a grant from the [http://www.vitiligoforbundet.se Swedish Vitiligo Association].

Vitiligo - in short

Vitiligo is a skin disorder causing affected parts of the skin to turn white. This is due to abnormal melanocyte function, resulting from the immune system mistakenly targeting the pigment cells, making Vitiligo an autoimmune disease. Vitiligo usually begins before the age of 20 and is estimated to affect 0.5-2 % of the world population. It is a very complex disorder and there is a lack of good treatments.

Spot on Treatment

iGEM Stockholm on the Vitiligo project This article is an effort from us in the iGEM Stockholm team to explain our Vitiligo-treatment scientific project in words that anyone can understand, consequently we will keep the scientific explanations on a basic level.

Our primary goal is to merge current scientific knowledge with an innovative new investigative approach known as Synthetic Biology, in order to hopefully help Vitiligo patients achieve faster and more efficient repigmentation of affected skin in the future.

Background

Vitiligo (leukoderma) is a skin disorder in which pigment cells known as melanocytes are destroyed, resulting in white patches of the skin1. Melanocytes are the cells responsible for creating skin color, so when these are destroyed, the normal shade of the skin turns white. Vitiligo is in itself not dangerous and does not lead to any severe health problems, but patients’ life quality may be seriously altered by the cosmetic appearance that is a result of the white spots from Vitiligo. Between 1-2 percent of the world population are estimated to be affected by Vitiligo, with varying levels of severity. The disorder is characterized by patches occurring on the skin in various parts of the body, hair growing on the patches may also turn white [1].

Population surveys have shown that Vitiligo patients first outbreak is seen before the age of 20 in 50 % of the cases, and 70-80 before the age of 30. So it is relatively uncommon with Vitiligo outbreaks in mid-age. Both sexes in adults and children are affected in equal weights; however studies have showed that females contact doctors in a larger number due to greater psychological and social impact [2].

At first, vitiligo can be thought of as a minor disorder, however the effect on patient’s self-esteem and social interactions can be devastating, especially in patients with darker pigmented skin where the white patches can be more visible. There are two distinguished large sub-sets of vitiligo, called focal/segmental vitiligo and non-segmental vitiligo. The former is characterized by few numbers of small lesions while the second form by an asymmetric distribution of the skin surface. Non-segmental vitiligo is correlated to all generalized, symmetrical forms. The course of the outbreak of the disease is unpredictable with phases of stabilized depigmentation. White vitiligo patches that are in an enlarging manner or the development of new lesions are classified as in an active form of disease [3].

Currently three major hypotheses of vitiligo have been proposed. The neural hypothesis implicates an accumulation of a neurochemical substance in the form of a toxin from nerve endings. This damages melanocytes and thus decreases melanin production. The biochemical hypothesis suggests an accumulation of toxic molecules from the synthesis of melanin in melanocytes, the breakdown of antioxidant molecules, and the build-up of large amounts of reactive molecules in pigment cells. Additionally, an autoimmune response in vitiligo patients has been proposed. Studies have demonstrated that vitiligo patients have developed antibodies and an activated immune system destructive against the body’s own pigment cells. Other possible causes of vitiligo have been suggested, including impaired melanocyte migration and/or development [3].

It might be that the mentioned factors act independently or together to result in the same effect, which is the disappearance of melanocytes from the skin [3].

Our research is divided up into two areas, which are long and short time effect on the skin. The long term research is focusing on both the biochemical and autoimmune hypothesis, which is to result in a repigmentation of white skin patches after a longer time period of treatment. The complementary short term research is based on repigmenting the affected patches in the similar effect of make-up while the long term treatment is under progress. This will be carried out by bacteria producing melanin on the skin, which will be absorbed and result in colored skin.

Our aim

Our research project uses harmless bacteria that, in fact, are already living in the human body as biological machines. These helpful bacteria are designed in our research project to become cost efficient machines to produce molecules that are deficient in vitiligo skin compared to normal skin. The goal with our project, until November 2010, is to obtain a “proof-of-concept” by having our bacteria produce and secrete molecules that we know, through previous research, are in a deficit in vitiligo skin. The lack of these specific molecules is thought to be involved in the impaired and disappeared pigment cells in vitiligo affected skin areas, leading to white spots.

Currently, there are not any treatments like ours for vitiligo skin. Our idea is to develop a treatment for vitiligo skin, where an ointment with harmless bacteria is to be produced for applying on white patched skin. The bacteria will synthesize and secrete several molecules of interest, which will then target specific inner skin cells with the aim of repigmentation.

One problem with this type of treatment is that the skin epidermis functions as a very efficient barrier against larger molecules. To help our potentially beneficial molecules reach their destination, we will therefore fuse them to special carrier molecules called cell-penetrating peptides (CPPs). As the name suggests, CPPs are small molecules that have the ability of penetrating into cells, but can in some cases also overcome the skin barrier. By fusing our molecules to such CPPs, we can let them hitch-hike over the skin barrier to the target area.

With our research we aim to in the future develop a treatment that works faster and more efficient in achieving a repigmentation on affected skin areas compared to current medicine.