Joshua Tycko is a postdoctoral research fellow at Harvard Medical School. His goal is to uncover how secreted proteins are routed to reach specific cell types to better understand how cells communicate and how those processes can be manipulated for genetic medicine. He received a Ph.D. in genetics from Stanford University where he developed a high-throughput recruitment approach that uncovered hundreds of human transcriptional effector domains that regulate gene expression. He and his collaborators also discovered new recombinases that can directly integrate large DNA into the human genome. Tycko previously worked in the biotechnology industry on measuring, modeling and mitigating CRISPR off-target activity to enable safer genetic medicines.

Tycko earned a bachelor’s degree in biological mathematics from the University of Pennsylvania, where he did undergraduate research on AAV gene therapy. He has served as a mentor to several undergraduate and graduate students and advised teams of undergraduate students in the iGEM synthetic biology competition. His research has been supported by NIH F99/K00 and NSF GRFP fellowships.

Principal Investigator: Michael Greenberg

Fellow: Luisa Quispe

Undergraduate Fellow Project:

The brain and other organs communicate by secreting thousands of proteins that travel throughout the body and activate receptors on target cells, forming a biological transportation network of protein packages that must be routed to their intended recipient cells. While some secreted proteins, such as insulin, have been deeply studied, we previously lacked tools to track a large number of proteins’ movement in an animal. For this project, we will use newly developed technology to ask fundamental questions such as: “Are there “passport” sequences that permit a protein to cross the blood-brain barrier?” Answering such questions will help us better understand how distal tissues communicate with the brain and better deliver synthetic proteins for therapeutic applications.

During this project, the SURFiN fellow will gain experience in molecular biology techniques including DNA plasmid design and cloning, CRISPR, protein purification and sequencing. We will use Python and Bash scripting to analyze and visualize biological datasets. In addition to their mentor, the fellow will also meet regularly with leading neuroscientist Michael E. Greenberg and benefit from the rich environment of postdocs, graduate students and other early career researchers in the Greenberg Lab.