Non-coding snoRNA Host Genes as novel therapeutic targets in atopic dermatitis and psoriasis

About the Project

Atopic dermatitis (AD, also known as eczema) and psoriasis are very common chronic inflammatory skin diseases marked by abnormalities in the functioning of the outer layer of the skin, the epidermis.

In these diseases, the balance between the self-renewal of epidermal stem cells and their differentiation into mature skin cells is disrupted. Both conditions are also characterised by the excessive activity of the immune system, with different signals involved in each, resulting in distinct but overlapping clinical features. Current therapies, such as biologics (antibody-based drugs) and topical corticosteroids, have limitations due to cost and side effects, highlighting the need for novel treatments[1,2].

Some parts of our genetic material, called long non-coding ribonucleic acids (lncRNAs), can control how skin cells grow and change. A group of lncRNA, called non-coding snoRNA Host Genes (ncSNHGs), is especially active in human epidermal cells (keratinocytes) and can help them keep dividing, while stopping their differentiation[3]. This activity can contribute to the symptoms we see in AD and psoriasis.

In this research, we want to understand if and how ncSNHG play a part in AD and psoriasis.

Since both diseases do not naturally occur in model organisms and ncSNHGs are only active in humans, we will use lab-grown human skin to test what happens when we lower the levels of these lncRNAs and see if this can restore a healthy balance in disease models.

We will then investigate the potential molecular mechanisms involved in the action of ncSNHGs by testing whether they affect the activity of small molecules called microRNAs, which are dysregulated in AD and psoriasis and can interact with ncSNHGs.

Finally, we will check if these findings match what is seen in patient skin samples.

If successful, this research could point the way to new, human-specific targets for the treatment of AD and psoriasis.

Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in the areas of cell biology, molecular biology. Candidates with experience in organotypic culture of primary cells (particularly keratinocytes) or with an interest in skin biology or RNA biology are especially encouraged to apply.

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cell Biology Programme. Full details on how to apply can be found on the Website.