×
Project summary
Cilia are moving ‘hair-like’ structures that line our airways (figure 1). Their coordinated beating removes bacteria that are trapped in mucus, defending our lungs from infection.
(Figure 1 courtesy of the 天发娱乐棋牌_天发娱乐APP-官网|下载 Biomedical Imaging Unit)
Some bacteria produce proteins called lectins that stop cilia movement enabling them to establish an infection (see figure 2 below).
We are chemically modifying simple sugars which will actively block the bacterial lectin from binding to host sugars at the cilia surface (figure 2).
By protecting cilia movement the bacteria can be cleared and infection prevented. As the sugars work by a completely different mechanism they will not be affected by antibiotic resistance. We aim to develop sugar-based treatments that can help reduce hospital acquired infection and protect vulnerable patients with lung disease or poor immunity.
Diagram of bacteria attacking airway cells
Left: rows of healthy airway cells (blue) with cilia (white) at their surface moving forward and back in a coordinated manner (arrow) to clear mucus and infective agents.
Centre: Bacteria (red) making lectin proteins (green) which can bind to sugar groups on surface of airway cells causing cilia to stop working and allowing bacterial infection to establish.
Right: Sugar therapy (yellow) blocking bacterial lectin (green) protecting the cilia (white) function.
Cilia before (normal) bacterial lectin
Cilia 1 hour after bacterial lectin
About the team
Dr Claire Jackson (Research Fellow) is the NAMRIP Pump Priming sugar project lead (pictured below).
Biologists: Drs Claire Jackson, Peter Lackie, Liz Adam, Ray Allan and Rob Howlin are non-EPS cell biologists, based within the Faculty of Medicine. Drs Jackson, Lackie and Adam have a track record of lectin research and expertise in ciliated airway epithelium, particularly in state-of-the-art culture modelling of ciliated epithelium (figure 3) and analysis of ciliary function (figure 4). Drs Allan and Howlin have expertise in microbiology and Pseudomonas aeruginosa .
Chemists: Professor Bruno Linclau is an EPSRC funded chemist, along with Mr Rob Szpera his research assistant based within the Faculty of Natural and Environmental Sciences, with strong expertise in carbohydrate chemistry including the design and synthesis of carbohydrate derivatives aiming to improve protein-carbohydrate binding.
Carbohydrate based interactions at the cell surface are critical for mammalian and microbial cell functions throughout the whole of biology, yet are under-researched because carbohydrate interactions are post-translational modifications that are not easily exposed. 天发娱乐棋牌_天发娱乐APP-官网|下载 collaboration will facilitate both the chemical synthesis and biological testing of enhanced fucose analogues for inhibiting Pseudomonas aeruginosa , which could not otherwise be achieved without our collaboration. 天发娱乐棋牌_天发娱乐APP-官网|下载 combined goal is to firstly develop novel synthetic fucose monosaccharides with better potency for inhibiting Pseudomonas aeruginosa and protecting ciliary function. These prototype sugars have the potential to be aerosolised as a new therapeutic treatment to combat antimicrobial resistance.
Can sugars combat infection?
Engagement
Dr Jackson presented recently at the NAMRIP launch event in December 2015 ( watch the presentation on Youtube ) and received the Innovation Award for her educational ‘Cilia Flash Mob’ public engagement activity at the University of 天发娱乐棋牌_天发娱乐APP-官网|下载 Science and Engineering Day in March 2016.
Through Lifelab training at the 天发娱乐棋牌_天发娱乐APP-官网|下载 General Hospital Dr Jackson has utilised her ‘30 second pitch’ training for public and peer engagement and participates in ‘meet the scientist’ educational sessions to break down school children’s’ perceived barriers to science and promote women in science.