Justin Bosch

RESEARCH:

Inter-organ communication via blood circulation

Organs “talk” to each other using hormones, growth factors, and cytokines in blood circulation. These “inter-organ” proteins regulate development, energy storage, and are important disease targets, but may be the tip of the iceberg. Blood plasma contains the equivalent of “dark matter” - thousands of circulating proteins with unknown functions. Many questions remain:

• Where do circulating proteins come from (i.e. cell-types)?
• Where do circulating proteins target (i.e. cell-type)?
• Which circulating proteins are inter-organ factors (and what is their function)?

My lab aims to answer these questions systematically using Drosophila, a model organism with human-like organ systems and precise tissue-specific genetic tools. Our goal is to broadly interlink organ systems by studying novel circulating inter-organ factors that are conserved throughout animal species, which has the potential to find therapeutic targets and biomarkers. We are studying several candidate inter-organ factors, including some that are released from, or target, the brain.

Tool development

Studying inter-organ factors systematically requires new tools to tackle the incredible complexity involved - a multitude of organ combinations (e.g. muscle -> fat, fat -> brain, etc.) and unknown numbers of factors in circulation. To address this, my lab develops:

• Tissue-specific proximity labeling (e.g. TurboID) paired with mass spectrometry (MS) to identify the origins and targets of circulating proteins.
• Genome engineering tools (e.g. CRISPR) to visualize and perturb candidate inter-organ factors.
• In silico protein complex prediction tools (e.g. AlphaFold) applied to discover inter-organ factors.

Importantly, these tools (e.g. genetically-encoded reagents) can be readily ported to other model organisms (e.g. zebrafish, mouse).

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