Molecular Insights into LINC Complex Proteins SUN1 and SUN2

Summer 2017

Darya Fadavi : Bioengineering

Mentor: Mohammad Mofrad

Transmission of cytoskeletal forces to the nucleus depends highly on the LINC (linker of the nucleoskeleton and cytoskeleton) complexes, which consists of inner nuclear membrane SUN (Sad-1 and Unc) proteins that bind to outer nuclear membrane KASH (Klarsicht, ANC-1, Syne Homology) proteins. Recent studies have suggested significant differences between SUN1 and SUN2 specifically in their homo-oligomerizaton in the perinuclear space. In my project, I use bioinformatics tools, molecular docking, and molecular dynamics (MD) simulations in collaboration with an experimental group to explore the molecular differences between these two proteins, SUN1 and SUN2. Narrowing my focus on SUN proteins 1 and 2 allows me to focus on a specific component of the multifaceted LINC complex, and by studying their structures and how they interact in MD simulations, I aim to identify key differences in their roles. Better understanding the differences between the members of the SUN family and their particular roles will help specifically identify how each member affects the different disease states connected to LINC complexes.

With the support of the SURF program and the Rose Hills Fellowship, I was able to commit myself this summer to my research project. This was the first time I had been able to do dedicated research, rather than it being a added activity alongside classes. This summer taught me what it means to actively pursue a research project, navigating pitfalls and unexpected results, and I wouldn't have been able to learn all that I did without the support of this fellowship. I'd like to extend my deepest thanks for all your support and your belief in me. Moving forward I am applying to medical school, but I will be carrying with me the lessons I learnt through research: to push on even in the face of seeming failure, and to explore multiple options before dedicating your resources to one to pursue.