Dr Dylan J M Bergen

I am interested in how the skeleton (cartilage/bone) is formed. The skeleton defines the shape of an organism and gives protection to vital organs (e.g. brain, lungs, and heart). In bone and cartilage elements, matrix is laid down in a specific way giving these skeletal tissues their specific characteristics (e.g. cartilage is spongy, bone is mineralised). Healthy bone is constantly remodelled (the complete human skeleton is slowly regenerated over ten years) to repair microfractures caused by loading of bone. This depends on a fine balance of bone building cells (osteoblasts and osteocytes) and bone degrading cells (osteoclasts) to maintain the right amount of bone.

The most common bone disease is osteoporosis which is diagnosed by assessing bone mineral caused using a DXA scan. Low bone mineral density is the parameter to diagnose osteoporosis, which affects ~50% of women and ~33% of men above the age of 55. Low bone mineral density is caused by a reduction in bone matrix caused by an altered balance of bone building cells and bone degrading cells. This results in brittle (porous) bones that fracture easily leading to serious, sometimes even life threatening, fractures in the hip, vertebrae, and long bones (ribs, femur etc.).

To better understand the biology of osteoporosis, my research makes use of large human genomic datasets (genome wide association studies, whole exome sequencing) to identify important genetic factors in the population that alter bone mineral density. I aim to find new osteoanabolic (stimulating osteoblasts and bone strength) genetic factors as current treatment options for osteoporosis mainly block osteocatabolic (osteoclasts à bone degrading) pathways. These unfortunately do not fully recover bone mineral density and bone strength.  

Large human genomic datasets of bone mineral density offer a great way to identify new bone mineral density genes however, these strategies produce 100s of potential genes. I am currently concluding a prioritisation pipeline to select the best candidates for studies in the lab, using the zebrafish model. The zebrafish allow relatively fast screening of these identified genes in a cost-effective way. I am working on the second part of the pipeline that involves zebrafish experiments to define the best osteoanabolic gene from these large human genomic studies.

I aim to use my scientific interest in the skeleton to integrate large genomic studies and functional studies in the lab, to define putative drug targets for osteoporosis.