Grant: Travel Awards - Institute Community Support

Chronic obstructive pulmonary disease (COPD) is a lung condition that affects people worldwide and is predicted to become the third cause of death globally by 2020. The frequent cause of COPD is cigarette smoking, although the disease continues to progress after stopping smoking. Its course is one of deteriorating breathlessness, frequent flare ups, poor quality of life, accelerated ageing and premature death. No curative treatment exists. In COPD, different cells in the lungs release various proteins that increase inflammation in the lung and other organs, thereby causing disease. While some of these proteins have been identified, we still do not fully understand their mechanism of action. Similar to the Human Genome Project which identified human genes in disease, it is imperative that we progressed and used a large scale method to identify the proteins these genes produce in COPD. This strategy is the only way we can develop investigations specific for diagnosing and monitoring COPD and develop new drugs that act on these proteins to halt disease progression. Several animal and human studies have shown that matrix metalloprotease-12 (MMP-12) causes COPD by digesting the proteins that make up lung tissue. Excitingly, a mouse lacking MMP12 has been bred these mice does not develop COPD thus providing a blank canvas which we can use to learn the role of MMP-12 in COPD. Our data shows that naturally occurring differences in human genetic make-up can make different forms of MMP-12. We suggest that some of these forms have more digestive activity and thus cause worse illness than less active MMP-12 forms. Our aims are 1) to identify which proteins are broken down by MMP-12; 2) to discover MMP-12 related proteins that are responsible for COPD; 3) to create differences in the MMP-12 gene to produce MMP-12 with different levels of digestive activity and how these differences affect protein breakdown; 4) to develop novel inhibitors for the treatment of COPD.