There are many critical scientific questions to be addressed in the field of life sciences. Here, two key scientific issues are introduced, which are expected to achieve groundbreaking results with the help of synchrotron radiation characterization techniques.

1. Research on Pathogen Identification, Pathogenesis, and Prevention/Control of Emerging Disease X

Emerging and re-emerging infectious diseases (typically represented by Disease X, mostly caused by viruses) are characterized by unclear pathogen origins and evolutionary pathways, complex cross-species transmission mechanisms, universal susceptibility in human populations, lack of early diagnostic technologies, and scarcity of specific prevention and treatment measures. Conducting original basic research on pathogen identification, pathogenic mechanisms, and prevention and control strategies, as well as establishing a reserve system of key technologies, is the core pathway to achieving proactive defense and holds strategic significance for strengthening the national biosecurity defense network.

  The users have utilized synchrotron radiation light source characterization technology to study the mechanisms of viral infection in cells and the development of antiviral drugs. For example, Valentina Loconte et al. employed full-rotation soft X-ray tomography (SXT) at the Advanced Light Source (ALS) to examine SARS-CoV-2-induced organelle remodeling at the whole-cell level with high spatial resolution and throughput (Cell Reports Methods,1, 7,2021,100117). Li Yang et al. utilized technologies such as soft X-ray imaging technique at the Hefei Light Source (HLS) to observe the cellular uptake, absorption, distribution, degradation, metabolism, and excretion of anti-COVID-19 drugs at the single-cell level. (Nature Nanotechnology ,17, 993–1003 (2022)).

However, there are still scientific questions needs to address are: 1) Achieving real-time observation of the life cycle of pathogens (viruses), 2) Enabling high-resolution in situ observation of virus-infected cells to capture changes in the structural morphology of host cells, alterations in the morphology and spatial organization of organelles, and interactions between pathogens (viruses) and organelles. Hefei Advanced Light Facility (HALF) is equipped with coherent imaging, coherent scattering, and mass spectrometry beamlines, offering advantages such as higher spatial resolution (3nm), higher detection sensitivity (ppb), and broad energy range coverage. These capabilities provide more powerful characterization tools for addressing the aforementioned scientific issues.

2. Analysis of Cellular Homeostasis Mechanisms and Intervention in Disease Progression

The imbalance of cellular homeostasis is a core mechanism underlying aging and related diseases (such as neurodegenerative diseases, cardiovascular diseases, metabolic diseases, cancer, etc.), involving dysregulation of various fundamental biological processes. Therefore, investigating the mechanisms of cellular homeostasis can help reveal the fundamental principles of life activities and advance precision intervention strategies based on organelle interactions and the regulation of the chemical microenvironment.

Currently, researchers have conducted characterization at the single-cell scale using synchrotron radiation facilities, investigating three-dimensional cellular structures, subcellular organelle architectures, and the interactions between drugs/nanomaterials and cells. The soft X-ray imaging technique in HLS enables users to image hydrated cells in their natural state, allowing direct observation of subcellular organelles and the intracellular localization and metabolism of nanomaterials/drugs. It provides a non-destructive characterization method for studying cellular behavior, while advancing sophisticated data reconstruction and processing techniques to help users efficiently extract precise and meaningful imaging information (Nat. Nanotech. 16(6):708,2021).

 HALF will provide imaging techniques with higher spatial and temporal resolution, offering a more powerful means for high-resolution dynamic characterization of single cells and delivering critical data to reveal the mechanisms of cellular homeostasis imbalance