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2019 Research Projects

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Research Project Descriptions

Investigating the reach of epigenetic inheritance mediated by disordered proteins

Intrinsically disordered proteins (IDPs) are ubiquitous in proteomes across the tree of life. Some of these IDPs have the remarkable ability to transduce environmental changes into traits that can be inherited for hundreds of generations. From a mechanistic standpoint, this epigenetic inheritance is driven by higher-order protein-assemblies called ‘prions’ that have distinctive biochemical hallmarks from their native states. Using a recently developed reporter to probe altered protein stability, we’ll be systematically investigating diverse proteomes to uncover the general principles associated with this mode of epigenetic inheritance.

Mechanistic dissection of novel regulators of phagocytosis

Phagocytosis is a conserved cellular process by which immune cells, such as macrophages, engulf and destroy a wide range of disease-causing targets, including cancer cells and neurotoxic aggregates. To systematically discover genes that regulate phagocytosis in different disease-relevant contexts, the Bassik laboratory has developed a platform, based on rapid magnetic separation of phagocytic cells, for conducting genome-wide CRISPR screens in human macrophages. Numerous novel phagocytosis regulators have been identified using this approach that may have important roles in regulating phagocytosis in different disease-relevant contexts. To uncover the mechanistic functions of these uncharacterized genes at a molecular level, we will identify the interaction partners of the these genes using both biochemical and genomic analyses and dissect their functions using quantitative microscopic assays.

The role of immune molecules (MHC class I) in activity-dependent neuronal plasticity

The brain develops with an exuberant number of connections, which are gradually refined with use to form discrete neuronal circuits. In the lab, we use the visual system as a model system to study synaptic pruning during early development, as well as in adulthood. Previously, the Shatz lab showed that MHC-I proteins, a family of immune molecules, are expressed in healthy neurons and have important functions in synaptic plasticity. This project involves characterizing functions for specific MHC-I molecules in health and disease.

Soft electrodes for brain implants

Long-term brain implants are important for understanding neural processing (e.g. memory), providing therapeutic treatment for diseases (e.g. Parkinson’s), and serving as brain-machine interfaces (e.g. controlling prosthetics). However, current long-term brains implants are hard, in contrast to soft brain tissue, and may lead to cell death and other problems. We have recently developed materials for soft brain implants and are currently inventing way to make functional devices and investigating their efficacy.

CRISPR-based epigenetic screening for advanced gene regulation

Our lab develops technologies for controlling biological function by co-opting CRISPR systems to tune gene expression within the cell (CRISPR activation / interference). Recently, a new CRISPR-based technology was reported to result in long-lasting gene silencing, but biological applications of this technology require further optimization and understanding of the system. This project will combine these advances with high-throughput screening to determine how widely useful this new gene regulation system is and how we can use it to most efficiently create durable gene knockdown. This knowledge can subsequently be used to perturb and explore cellular processes such as differentiation, cell growth, and immunological function.

Mechanotransduction at the biomedical implant-tissue interface

The lab's focus lies at the interface of bioengineering, surgery and data science, exploring the role of mechanotransduction in biomedical implant rejection. We use various techniques and resources ranging from in vitro experiments and animal models to clinical samples and data science-based tools to understand biomedical implant rejection and develop therapies to improve implant lifetimes. 

Identifying novel circulating biomarkers of cardiomyopathy using iPSC-cardiomyocyte derived exosomes

Cardiomyopathy is a disease of the heart that can lead to life threatening heart failure. If detected early, physicians can start medications and use devices to improve symptoms and prolong life. Our laboratory is searching for new biomarkers of heart failure by studying the microparticles secreted from the heart. To do this, we will generate heart tissue from patients using stem cells and utilizing a novel engineering approach, we will isolate microparticles and compare their contents with patient blood and identify novel biomarkers to diagnose cardiomyopathy.