Dr Aimée Bugler-Lamb

Project Title: Role of Adipose ß-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) in Insulin Resistance

The extracellular matrix (ECM) consists of various macromolecules surrounding the cells within a tissue of which the primary molecules are collagens, proteoglycans and glycoproteins. It is essential for the structure of tissues, as it provides scaffolding and supports the cells. It is now acknowledged that the ECM also influences individual but also collective cellular behaviour such as differentiation, migration and survival.

The main substrate-molecule linking the ECM to the intracellular signalling pathways are integrins, which are transmembrane proteins, composed of and  subunits and have a large extracellular domain and a small intracellular domain. Integrins have been shown to be regulated by multiple proteins, however one of the most important regulators of integrins is the protein ILK (integrin linked kinase). The integrin-linked kinase (ILK) is widely expressed throughout the body carrying out multiple functions and is known for its role as an adaptor protein to allow the communication between the ECM and the surrounding cells.

Integrin-linked kinase (ILK), Parvin and PINCH form a heterotrimeric complex called the IPP complex where ILK is considered as the main protein as it binds both parvin and PINCH as well as the cytoplasmic tail of -1 and -3 integrins. It has previously been shown that deletion of ILK in skeletal muscle decreases insulin resistance and inflammation. As adipose tissue expands through increased energy intake (obesity), the ECM remodels leading to increased inflammation and decreased vascularisation.

Hypothesis: As adipose tissue is greatly affected by obesity, we hypothesis that tissue-specific knock down of ILK in adipose tissue will result in increased insulin sensitivity and decreased inflammation in mice.

Research aims

AIM 1:  Investigating the effects of ILK on inflammation and insulin resistance

AIM 2: Investigating a potential role of ECM remodelling in the metbolic regulation of adipose BACE1 in inflammation and insulin resistance in mice in vivo

AIM 3: Investigate the ECM remodelling in human adipose tissue.

Aimée Bugler-Lamb is a Carnegie PhD Scholar in the Division of Cardiovascular & Diabetes Medicine at the University of Dundee. Her work is supervised by Dr Li Kang, Discover Fellow, whose research investigates the pathogenesis of insulin resistance.