Dr Michael Lethem

Senior Lecturer

contact:
Pharmacy and Biomolecular Sciences
Moulsecoomb
Brighton
BN2 4GJ

Telephone: +44 (0)1273 642046

Email: M.I.Lethem@brighton.ac.uk

Research Interests

• Epithelial cell biology
• Regulation of airway secretion
• Cystic fibrosis
• Asthma
• Chronic bronchitis
• Biochemistry and rheology of mucus secretions

Research into Respiratory Diseases:

My principal research interests are in airway epithelial function in health and disease, in particular mucociliary function. Mucociliary clearance is the principal non-specific defence mechanism of the airways and acts in the upper airways to entrap particles and other inhaled materials in mucus and transport them from the lungs. Efficient mucociliary transport is the result of the co-ordination of airway three epithelial functions, mucus secretion, ciliary beat and ion and fluid transport (See Figure 1 for cartoon of airway epithelium and, Figure 2 for micrograph of isolated airway epithelium showing cilia and dark staining goblet cells)

Figure 1: Cartoon of airway epithelium

Figure 2: Micrograph of isolated airway epithelium showing cilia and dark staining goblet cells

Many of the cells lining the upper regions of the airways possess cilia which beat in a co-ordinated manner within a film of liquid (Periciliary Fluid), and in doing so move the overlying mucus over the surface and up out of the airway.

Cilia Video – Click to see a video of airway epithelium with beating cilia. (windows media player)

Mucociliary Transport Video - Click to see a video showing fine carbon particles being transported across the surface of airway epithelium by mucociliary transport. (windows media player)

In a healthy airway this process removes unwanted inhaled materials and protects the delicate lower airways where gas exchange occurs. However, in some situations, alteration in one or more of the components of this mucociliary clearance system result in impaired mucociliary transport with a resultant reduction in airway defence. This loss of mucociliary function is frequently associated with the accumulation of mucus in the airways, which commonly leads to airway obstruction, a predisposition to respiratory infections and further mucus secretion. As a result the diseases in which this occurs are those characterised by airway obstruction and mucus hypersecretion e.g. cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD).

The work in my laboratory aims to use cell and molecular biology approaches to understand the regulation of the individual elements of mucociliary function (mucin secretion, ciliary activity and ion and fluid transport). The group has developed several novel model systems of the airway epithelium and, using these, has recently identified the first physiological mechanism for inhibiting mucin secretion from airway goblet cells. This finding may open up novel opportunities for reducing mucus production in diseases such as COPD. In addition we have recently developed a high-speed digital videomicroscopy system which permits the measurement of ciliary beat frequency, and this is currently being used to investigate potential mechanisms regulating ciliary activity. Facilities are available for bioelectric studies using Ussing chambers to investigate ion transport processes across the airway epithelium. The knowledge gained from these studies can be related to changes in mucociliary function in disease as well as being used to try and identify possible therapeutic approaches to treating these diseases.

The laboratory also has collaborations with other academic groups in the UK and USA as well as industrial laboratories. Our work has been supported by grants from several sources including the Wellcome Trust, Biotechnology and Biological Sciences Research Council and the pharmaceutical industry.

Research Publications