Optogenetic Control of Membraneless Organelle Formation

University of Pittsburgh researchers have developed a novel method for the optogenetic induction of membraneless organelles using blue light stimulation. This technique allows for the temporal and spatial control of organelle formation, enabling researchers to study the dynamics and functions of these structures in various cellular processes and diseases. The technology has significant implications for understanding the role of membraneless organelles in neurodegenerative diseases, cancer, and other conditions, and offers a powerful tool for drug screening and basic science research.

Description

The technology involves the use of DNA arrangements consisting of photoreceptor domains (CRY2 or LOV) that cluster or homodimerize in response to blue light exposure. These photoreceptor domains are fused to proteins containing low complexity domains (LCDs) or intrinsically disordered regions (IDRs), which are key components of membraneless organelles. Upon blue light stimulation, the fusion proteins undergo liquid-liquid phase separation (LLPS), leading to the formation of functional membraneless organelles. This method allows for precise control over the formation and dynamics of these organelles, providing a unique platform for studying their roles in cellular processes and disease pathobiology.

Applications

- Research tool for studying membraneless organelles
- Investigation of neurodegenerative diseases (e.g., ALS, Alzheimer’s, Parkinson’s)
- Cancer research
- Drug screening and development

Advantages

This technology offers a novel approach to studying membraneless organelles by enabling their formation and control using optogenetics. The ability to induce organelle formation with blue light provides temporal and spatial precision, allowing researchers to investigate the dynamics and functions of these structures in real-time. This method can be applied to various cytoplasmic and nuclear organelles, making it a versatile tool for studying a wide range of cellular processes and diseases. Additionally, the technology can be used for high-throughput drug screening, providing a platform to identify compounds that modulate organelle function.

Invention Readiness

The technology is currently at the in vitro data stage, with successful demonstration of light-induced stress granule formation in HEK cells. The researchers have shown that the photoreceptor domains (CRY2 and LOV) can induce the formation of functional stress granules upon blue light exposure. These light-induced stress granules colocalize with key stress granule components and exhibit characteristics similar to naturally occurring stress granules.

IP Status

https://patents.google.com/patent/US20200224204A1