Tyler Camp, PhD
Name of Institution:
University of Illinois Urbana-Champaign, Champaign, IL
α-synuclein oligomerization and membrane localization in Parkinson’s disease
Tyler Camp received his B.S. in Computer Science from the University of Texas at Austin. He received his Ph.D. in Biophysics and Quantitative Biology from the University of Illinois at Urbana-Champaign under the supervision of Dr. Stephen Sligar. While working as a graduate student, Dr. Camp applied fluorescence methods to study protein-lipid interactions in the context of cancer signaling and drug metabolism. In 2021, he joined the laboratory of Dr. Kai Zhang at University of Illinois at Urbana-Champaign as a postdoctoral scientist to develop new cellular and animal models of Parkinson’s disease (PD) with an eye toward improving our understanding of disease pathogenesis.
To understand how the size and location of α-synuclein clusters affects its toxicity
The brains of patients diagnosed with PD are known to contain large clumps of proteins called Lewy bodies. α-synuclein is the most abundant protein in these clumps and mutations in this protein are a known genetic risk factor for developing PD. Despite this, it is unknown how (or even if) the clumping of this protein causes disease. It is also unclear whether the size of the clumps impacts their harmfulness in living cells. While scientists originally thought that large clusters caused the greatest damage, new research has shown that smaller clumps might be more damaging. Additionally, the association of α-synuclein with cellular membranes, which separate the cell from its external environment, is thought to influence toxicity, but whether this interaction contributes to disease progression is an open question.
We created a system that allows us to induce the clumping of α-synuclein in living cells by illuminating them with light. We built these tools by fusing α-synuclein with another protein that clusters in response to blue light. Importantly, this will allow us to vary the amount of clustering by varying the light intensity and exposure time without changing the total amount of protein. We can also measure the approximate size of these clusters using microscopy. By controlling the amount of clustering and relating the cluster size to cellular damage we will solve an important problem in understanding how PD pathology might be initiated or progress. We are also developing methods to bring α-synuclein to cellular membranes in response to light. This will allow us to study the interaction between α-synuclein and cellular membranes. Finally, we will use computer simulations to study how α-synuclein clusters interact with cell membranes and how these interactions are changed by the electrical charge on the membrane.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Understanding the relationship between α-synuclein cluster size and toxicity will provide much needed guidance for developing treatments for PD. For example, if our work reveals that smaller clusters are more harmful, this knowledge will guide drug development and therapeutic efforts toward eliminating smaller clusters rather than targeting larger ones. On a more fundamental level, understanding how cluster size impacts its potential to do damage, will give clues to how PD might be initiated or evolve. Experiments that target α-synuclein to cell membranes will also help us understand whether these interactions are harmful and allow us to design therapies to limit toxicity.