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Justin Bosch

Assistant Professor of Human Genetics

Cell Signaling, Genetics, Development, Inter-organ Communication, Drosophila, CRISPR, Plasma Proteomics

Justin Bosch

 

Molecular Biology Program

Education

B.S. University of Wisconsin–Madison

Ph.D. University of California, Berkeley

 

 

Research

Our lab studies inter-organ communication via proteins in blood circulation (e.g. hormones). We are interested in answering long-standing questions such as:

  • Where do circulating proteins come from and where do they go? (i.e. cell-types)
  • Which proteins mediate inter-organ communication?
  • What is the binding specificity of inter-organ molecules? (e.g. hormones)

 By mapping protein networks between organs, discovering novel circulating factors, and applying new approaches to well-studied hormones, we aim to understand basic mechanisms of inter-organ communication, improve disease diagnosis, and identify therapeutic targets and biomarkers for human diseases.

We use a combination of experimental and computational tools, including protein proximity labeling (e.g. TurboID) to map the origins and destinations of blood proteins, mass spectrometry of blood plasma, in-silico biomolecular interaction screens (e.g. AlphaFold), and genome engineering tools (e.g. CRISPR) to visualize and perturb candidate inter-organ factors. For in-vivo experiments, we use Drosophila, a model animal with human-like organ systems and precise tissue-specific genetic tools.

fig1

Inter-organ mapping

Circulating hormones that bind receptors play key roles in inter-organ communication, but their discovery using traditional experimental approaches has been slow and incremental. Recent advances in proximity labeling enzymes and AI-driven protein structure modeling now enable large-scale unbiased mapping of inter-organ communication. Our lab is adapting these new tools and developing our own to study inter-organ communication.

Proximity labeling enzymes are powerful tools to map the origins and destinations of secreted proteins in vivo. During Dr. Bosch’s postdoc, he showed that TurboID is an effective proximity labeling tool in live Drosophila tissues (Branon et al. 2019Droujinine et al. 2021). More recently, he applied TurboID to identify the origins of secreted proteins from 10 major tissue types, revealing an unprecedented tissue-secretome map of proteins in circulation (Bosch et al. 2025), and candidate inter-organ factors (below). Our lab is adapting this tissue-secretome mapping technique to disease models to identify tissue-specific induced factors that promote or prevent disease pathology. We are also developing new proximity labeling approaches to map and discover inter-organ proteins, such as tissue “receive-ome” tools that complement our existing tissue secretome approach.

Recent advances in AI models now enable in-silico prediction of biomolecular interactions (PPIs), facilitating large-scale, high-throughput screens for novel hormone-receptor pairs. Unfortunately, these in-silico screens are computationally prohibitive. Our lab developed an efficient computational pipeline using GPUs at the University of Utah Center for High Performance Computing (CHPC), which dramatically reduces computation time, expense, and manual intervention. Our lab is screening hundreds of thousands of Drosophila hormone-receptor pairs and have uncovered interesting candidates (see below). This unbiased in-silico screen provides new steps toward an unprecedented systems-level view of inter-organ communication that complements our proximity labeling approaches. We are also working to make our in-silico interaction screens more efficient and take advantage of ever improving software tools.

We are looking for new members with experimental or computational experience to spearhead these high-risk high-reward discovery projects. These projects are most suitable for post-docs. 

fig2

[Image] Drosophila larvae expressing the proximity labeling enzyme TurboID in 10 different cell types

Studying novel inter-organ factors

Many candidate inter-organ factors came out of our inter-organ ‘omics’ screens (above), and current projects in the lab involve characterizing these factors in Drosophila. For example, we are studying two secreted factors that independently regulate body size, implying systemic roles. In addition, we are studying a circulating protein that we believe targets neuronal synapses and regulates synaptic strength. Current and future screens will continue to generate new inter-organ factors for molecular characterization.

We are recruiting new members to take ownership over an inter-organ factor, and in some cases have the privilege to give them a name. These projects are most suitable for graduate students as they have a clear roadmap toward a publication.

fig3

[Image] Drosophila wing imaginal disc showing localization of a candidate inter-organ factor (green)

Genetic tool development

Characterizing inter-organ factors in vivo requires a panel of genetic reagents (i.e. transgenic flies) including gene knock-out, knock-in, overexpression, RNAi, and protein tagging. In Dr. Bosch’s post-doc, he developed CRISPR/Cas9 methods to generate these reagents faster (Bosch et al. 2020Bosch et al. 2021Bosch et al. 2022Bosch et al. 2023Zirin et al. 2024). Our lab employs several plasmid cloning and transgenic pipelines and adapts and develops new gene editing tools for Drosophila, such as improved methods to make DNA base changes or insert large DNA.

We are looking for graduate students and post-docs members that will pursue genetic tool-focused projects as a side project to complement their primary biological project, or for an undergraduate main project.

fig4

[Image] Wild-type (left) and transgenic (right) Drosophila pupae.

Hormone-receptor binding specificity

Hormones “signal” by binding receptor proteins, but the molecular rules of binding specificity is not fully understood. For example, pathogenic missense variants can disrupt hormone-receptor binding, but we currently can’t yet predict all missense variants that disrupt binding. Furthermore, it’s possible that non-canonical “crosstalk” binding between hormones and receptors has been overlooked. Our lab is using in-silico binding approaches (e.g. AlphaFold) to map and discover hormone-receptor binding specificity and validate our predictions in cell and animal models. We expect broad impact, including deeper insight into hormone-receptor biology and improving the interpretation of missense variants in patient genomes.

For example, we are modeling the effects of missense mutations on hormones-receptor binding specificity. Pilot efforts of saturation mutagenesis of the Insulin-Insulin Receptor (Ins-InsR) identified missense mutations that are predicted to disrupt binding and are known to be pathogenic in humans. We are also systematically testing and exploring the landscape of alternative hormone-receptor binding (aka crosstalk signaling). By screening thousands of possible pairs, we identified several non-canonical human hormone-receptor pairs for follow-up.

We are currently focusing these efforts on human hormone-receptors and anticipate results from this project will feedback into Drosophila projects to study basic mechanisms.

We are looking for a post-doc and/or graduate student to pursue this project. Particularly with a background in structural biology and/or medical genetics. Perhaps most appropriate for a MD-PhD student.

fig5

Selected Publications

  1. Justin A. Bosch, Pierre Michel Jean Beltran, Cooper Cavers, James Thai LaGraff, Randy Melanson, Ankita Singh, Weihang Chen, Yanhui Hu, Sudhir Gopal Tattikota, Ying Liu, Yousuf Hashmi, John M. Asara, Tess Branon, Alice Y. Ting, Steven A. Carr, Norbert Perrimon. Multi-omic mapping of Drosophila protein secretomes reveals tissue-specific origins and inter-organ trafficking. bioRxiv. [link]
  2. Abby V McGee, Yanjing V Liu, Audrey L Griffith, Zsofia M Szegletes, Bronte Wen, Carolyn Kraus, Nathan W Miller, Ryan J Steger, Berta Escude Velasco, Justin A. Bosch, Jonathan D Zirin, Raghuvir Viswanatha, Erik J Sontheimer, Amy Goodale, Matthew A Greene, Thomas M Green, John G Doench. Modular vector assembly enables rapid assessment of emerging CRISPR technologies. bioRxiv 2023.10.25.564061; In press at Cell Genomics.
  3. Jonathan Zirin, Barbara Jusiak, Raphael Lopes, Ben Ewen-Campen, Justin A. Bosch, Christians Villalta, Corey Forman, Yanhui Hu, Stephanie Mohr, Norbert Perrimon (2024). Expanding the Drosophila toolkit for dual control of gene expression. eLife 12:RP94073
  4. Justin A. Bosch, Keith N, Escobedo F, Fisher WW, LaGraff JT, Rabasco J, Wan KH, Weiszmann R, Hu Y, Kondo S, Brown JB, Perrimon N, Celniker SE. Molecular and functional characterization of the Drosophila melanogaster conserved smORFome. Cell Rep. 2023 Oct 26;42(11):113311. doi: 10.1016/j.celrep.2023.113311. Epub ahead of print. PMID: 37889754.
  5. Justin A. Bosch, Berrak Ugur, Israel Pichardo-Casas, Jorden Rabasco, Felipe Escobedo, Zhongyuan Zuo, Ben Brown, Susan Celniker, David Sinclair, Hugo Bellen, and Norbert Perrimon. (2022) Two neuronal peptides encoded from a single transcript regulate mitochondrial complex III in Drosophila. 2022 Nov 8;11:e82709. PMID: 36346220
  6. Droujinine IA, Meyer AS, Wang D, Udeshi ND, Hu Y, Rocco D, McMahon JA, Yang R, Guo J, Mu L, Carey DK, Svinkina T, Zeng R, Branon T, Tabatabai A, Justin A. Bosch, Asara JM, Ting AY, Carr SA, McMahon AP, Perrimon N. (2021) Proteomics of protein trafficking by in vivo tissue-specific labeling. Nature Communications. Apr 22;12(1):2382. PMID: 33888706
  7. Justin A. Bosch, Gabriel Birchak, Norbert Perrimon. (2021) Precise genome engineering in Drosophila using prime editing. Proceedings of the National Academy of Sciences. Jan 5;118(1):e2021996118. PMID: 33443210
  8. Justin A. Bosch, Chiao-Lin Chen, and Norbert Perrimon. (2021) Proximity-dependent labeling methods for proteomic profiling in living cells: An update. Wiley Interdisciplinary Reviews: Developmental Biology. Jan;10(1):e392. PMID: 32909689
  9. Justin A. Bosch, Shannon Knight, Oguz Kanca, Jonathan Zirin, Donghui Yang-Zhou, Yanhui Hu, Jonathan Rodiger, Gabriel Amador, Hugo J. Bellen, Norbert Perrimon, Stephanie E. Mohr. (2020) Use of the CRISPR-Cas9 system to introduce fluorescent tags into endogenous genes in Drosophila cultured cells. Current Protocols in Molecular Biology. Mar;130(1):e112. PMID: 31869524
  10. Justin A. Bosch, Ryan Colbeth, Jonathan Zirin, Norbert Perrimon. (2020) Gene knock-ins in Drosophila using homology-independent insertion of universal donor plasmids. Genetics. Jan;214(1):75-89. PMID: 31685521
  11. Tess C Branon, Justin A Bosch, Ariana D Sanchez, Namrata D Udeshi, Tanya Svinkina, Steven A Carr, Jessica L Feldman, Norbert Perrimon, Alice Y Ting. (2018) Directed evolution of TurboID for efficient proximity labeling in living cells and organisms. Nature Biotechnology. Oct;36(9):880-887. PMID: 30125270
  12. Justin A. Bosch, Taryn M. Sumabat, and Iswar K. Hariharan. (2016) Persistence of RNAi-Mediated Knockdown in Drosophila Complicates Mosaic Analysis yet Enables Highly Sensitive Lineage Tracing. Genetics. May;203(1):109-18. PMID: 26984059
  13. Justin A. Bosch, Ngoc Han Tran and Iswar K. Hariharan. (2015) CoinFLP: A system for efficient mosaic screening and for visualizing clonal boundaries in Drosophila. Development. Feb 1;142(3):597-606. PMID: 25605786
  14. Justin A. Bosch, Taryn M. Sumabat, Yassi Hafezi, Brett J, Pellock, Kevin D. Gandhi and Iswar K. Hariharan. (2014) The Drosophila F-box protein Fbxl7 binds to the protocadherin fat and regulates Dachs localization and Hippo signaling. Aug 8;3:e03383. PMID: 25107277
Last Updated: 7/29/25