Katherine Souter

Supervisor: Daniel Graf

Project: Bone morphogenetic protein-2 (BMP2) in cranial sutures - more than just bone formation

Hometown:

Kitimat, BC

Degree program:

Bachelor of Science with Honors in Neuroscience

Why did you choose the degree program you are in?

I have always been fascinated by the brain, but I decided to pursue a neuroscience degree when I saw the impact neurodegenerative diseases had on my family. I hope to complete a PhD in neuroscience and attend medical school so I can make a meaningful impact on those affected by neurological conditions, as well as provide support for their loved ones.

How would you describe your research project to someone without a scientific background in one or two sentences?

I have been studying the role of two proteins, BMP2 and BMP7, in the formation of the bones that surround the brain (visible skull bones and the base of the skull beneath the brain). Normal growth of these bones is critical to provide sufficient space for the brain and to ensure that the spinal cord and nerves can pass through.

What's been the best part of your experience so far?

I love working in a lab with so many incredible people and learning many new things about research and the field of craniofacial development. Everyone in the lab has been supportive throughout my project and they have taught me many invaluable lab techniques that I can apply to my future studies. Participating in research has also deepened my appreciation for the field of science and all of the work that goes into these important discoveries.

What were your results?

After performing an immunofluorescence experiment to see BMP2 and BMP7 expression at various stages in skull development, it seems as though these proteins play a role very early on that sets up the cranial base for proper development. These proteins seem to act in different places and at different times in the cranial base, which is really exciting and will guide us in planning future experiments to better understand the role of these proteins in the cranial base.

What's one piece of advice you received from your supervisor/mentor that resonated with you?

In the lab, I have been encouraged to try new techniques and come up with theories to explain the observations I make. Dr. Graf has taught me not to be afraid to think outside the box and learn something new, as well as to always ask for help when needed. I have learned so many valuable skills and lessons from my time in the Graf Lab, primarily because it is a wonderful learning environment with incredible people who are passionate about their work.

Lay abstract:

Postnatal skull growth occurs primarily at sutures, the fibrous connections between skull bones. Sutures allow the translation of mechanical pressure from the growing brain into signals for stem cell differentiation to form new bone. In humans, sutures eventually fuse (suture obliteration). Craniosynostosis involves premature suture obliteration and is associated with a lopsided skull. Currently, we lack a good understanding of what keeps sutures patent (unfused) and how mechanical cues translate into bone growth. In another region of the skull, the cranial base supports the brain from below. While sutures are related to intramembranous ossification—bone development from fibrous membranes—the cranial base involves endochondral ossification—bone development by replacing cartilage.

Bone morphogenetic protein-2 (BMP2) has been linked to bone formation and increased risk for premature bone fusion, but its role in sutures is less clear. We already know bone morphogenetic protein (BMP) signalling promotes bone growth, while BMP antagonists maintain unfused sutures. 

Last summer, I discovered stronger BMP2 expression in sutures after growth was complete, which suggests a role for BMP2 in suture maintenance rather than solely bone formation. This discovery provides a novel angle to study suture patency and bone growth. I hypothesize that BMP2 has a biphasic role in sutures: an early role to establish the suture and a later role in suture maintenance by inhibiting suture obliteration.

This summer, I propose a detailed craniofacial characterization of BMP2 neural crest knockout animal model, where BMP2 has only been deleted from neural crest-derived cells. I aim to identify structures requiring BMP2 to explain cellular processes dependent on BMP2. I will describe BMP2 in both suture and cranial base establishment, growth and maintenance. To assess if/how BMP2 directly affects bone formation, I will culture BMP2-deficient osteoblast precursors, which are essential for osteoblast bone formation, to assess molecular changes in bone formation, as osteoblasts are key to bone growth.

This project allows an investigation of molecular and cellular events in suture establishment and maintenance, as well as cranial base development.