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Abstract

Untangling the Microscopic World of Organelles, Cells, Tissues, and Organs: A Focus on the Dysfunctional Golgi Apparatus in Disease Research †

1
SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA
2
Department of Biological Sciences, California State University, East Bay, Hayward, CA 94542, USA
Presented at Cells, Cells and Nothing but Cells: Discoveries, Challenges and Directions, 6–8 March 2023; Available online: https://cells2023.sciforum.net/.
Biol. Life Sci. Forum 2023, 21(1), 15; https://doi.org/10.3390/blsf2023021015
Published: 21 March 2023

Abstract

:
Emerging techniques in organelle structural biology have revolutionized our understanding of disease mechanisms and opened new possibilities for developing targeted therapies. In particular, dysfunctions of the Golgi apparatus (GA) have been implicated in a wide range of neurological disorders and cancer, making it a key area of focus in organelle structural biology. The GA plays a crucial role in regulating the transport and modification of proteins and lipids, and dysfunction of this organelle can lead to mislocation and accumulation of proteins and impaired glycosylation, resulting in neurodegenerative diseases such as Parkinson’s Disease and neurodevelopmental disorders (NDDs). Inhibition of vesicular trafficking by α-synuclein may affect dopamine-producing neurons and neuromodulators, while fragmentation and defects within the GA can lead to apoptotic pathways during pathological mechanisms. Additionally, defects and fragmentation of the GA have been implicated in cancer progression, making it a key area of interest for cancer researchers. Advances in imaging technology, such as cryogenic electron tomography, soft-X-ray tomography (SXT), and multiplex correlative light and electron microscopy (CLEM), have enabled high-resolution visualization of the GA and its dysfunctions in neurological diseases and cancer. These techniques provide detailed insight into the structure and function of the GA and have the potential to inform new treatments for diseases associated with GA dysfunction. Recent studies have shown that molecular zippers hold the Golgi membrane together, providing further insight into the mechanisms underlying GA dysfunction in diseases such as Parkinson’s, NDDs, and cancer. Cryo-CLEM and nanobody-assisted tissue immunostaining for volumetric EM (NATIVE) techniques enable high-resolution visualization of the GA and its native environment, aiding in understanding its function in health and disease. In addition, novel techniques such as Optical coherence tomography (OCT) enable rapid, accurate, and high-resolution in vivo imaging of the mouse cortex, providing 3D visualization of cortical microarchitecture using a feature segmentation algorithm. OCT enables label-free, micron-scale 3D imaging of biological tissues’ fine structures with significant depth and a large field of view. A 3D CNS segmentation mask of brain neural networks in a living mouse can be visualized at micron-level resolution using OCT. Overall, the organelle structural biology field, specifically the study of the Golgi apparatus dysfunction in neurological disorders and cancer, has significant implications for developing new therapeutic targets, gene therapy, and drug design. With continued research and advancements in imaging technologies, we can expect to gain a more comprehensive understanding of the underlying mechanisms of GA dysfunction in neurological disorders and cancer, paving the way for innovative new treatments and therapies.

Graphical Abstract

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data is available at https://doi.org/10.20944/preprints202210.0383.v2 (accessed on 17 March 2023).

Acknowledgments

D.J.G. thanks members of the SSRL, SLAC, and LCLS and associated laboratories for helpful discussions.

Conflicts of Interest

D.J.G. is the Director of Multiomics in the Multiomics Structural Biology and Network Physiology Division, Neuro-Spatial Multi-Omics Structural Biology (NSMOSB) unit at Gomera Research. As the Lead Molecular Research Scientist and Biomedical AI/ML Engineer at Gomera, D.J.G. works on spatial multi-omics, quantum computational medicine, and machine learning. Additionally, D.J.G. is the founder and has equity in Gomera Health, Inc. and GomeBio LLC, and serves as a scientific advisory board member for Gomera Health, Inc.
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MDPI and ACS Style

Gómez, D.J. Untangling the Microscopic World of Organelles, Cells, Tissues, and Organs: A Focus on the Dysfunctional Golgi Apparatus in Disease Research. Biol. Life Sci. Forum 2023, 21, 15. https://doi.org/10.3390/blsf2023021015

AMA Style

Gómez DJ. Untangling the Microscopic World of Organelles, Cells, Tissues, and Organs: A Focus on the Dysfunctional Golgi Apparatus in Disease Research. Biology and Life Sciences Forum. 2023; 21(1):15. https://doi.org/10.3390/blsf2023021015

Chicago/Turabian Style

Gómez, Daniel Joseph. 2023. "Untangling the Microscopic World of Organelles, Cells, Tissues, and Organs: A Focus on the Dysfunctional Golgi Apparatus in Disease Research" Biology and Life Sciences Forum 21, no. 1: 15. https://doi.org/10.3390/blsf2023021015

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