As the seasons turn and the Spring Festival draws near, SMART presents a special gift of "New Year Research Hights" to all, wrapped in the festive spirit of joy and harmony. Looking back on 2024, SMART embraced the spirit of bold innovation -- breaking down barriers, sparkling creativity, and steadily enhancing its research capacity. Our dedicated research teams delved deep into work with meticulous dedication, achieving a series of remarkable scientific breakthroughs. We've curated some of the most representative research accomplishments to showcase SMART's journey of innovation and breakthroughs over the past year. 

Novel Solutions

Breaking Technical Bottlenecks: Novel Approaches Unlock Fresh Insights

Dr. Mingxu Hu's team and collaborators proposed two innovative algorithms for cryo-electron microscopy (cryo-EM) image processing, injecting new momentum into the field and advancing the development and application of related technologies.

Dr. Mingxu Hu's team and collaborators developed CryoSieve, a novel tool designed to tackle critical challenges in amplitude optimization.

On December 10, 2023, Dr. Mingxu Hu's team and collaborators published a research paper titled "A minority of final stacks yields superior amplitude in single-particle cryo-EM" in Nature Communications. To address the long-standing challenge in cryo-electron microscopy (cryo-EM) that the number of particles required for structural reconstruction far exceeds theoretical expectations, the team developed an innovative iterative particle selection method called CryoSieve. Their findings revealed that a small subset of particles in the final dataset can yield superior amplitude in cryo-EM reconstructions. This study was selected as one of the "Top 25 Most Popular Physics Articles of the Year" by Nature Communications, drawing significant attention from the global cryo-EM research community.

Dr. Mingxu Hu's team and collaborators have proposed an innovative algorithm that enables the computation of spatial orientation under the framework of molecular symmetry groups.

On November 5, 2024, Dr. Mingxu Hu's team and collaborators published a research paper titled "Averaging Orientations with Molecular Symmetry in Cryo-EM" in the internationally renowned journal SIAM Journal on Imaging Sciences. This study introduces an innovative algorithm that enables the computation of the mean and variance of spatial rotations and projection directions under the framework of molecular symmetry and demonstrates its application in visualizing asymmetric features in two-dimensional data.

Novel Discoveries 

Probing Life's Mysteries: Novel Pathways for Disease Treatment

Dr. Xiaojing Pan's team elucidates the structure and functional mechanisms of the gout-associated transporter GLUT9 through structural biology approaches.

On June 12, 2024, Dr. Xiaojing Pan's research team published a research paper in Nature Communications titled "Structural basis for urate recognition and apigenin inhibition of human GLUT9." GLUT9 is a key therapeutic target in the treatment of hyperuricemia and gout. Using structural biology approaches, the team uncovered the molecular mechanisms underlying the binding of GLUT9 to its substrate urate and the natural small-molecule inhibitor apigenin. This work lays the molecular foundation for understanding substrate selectivity and for developing small-molecule inhibitors targeting GLUT9.

The activation mechanism of key receptor molecules in allergic reactions has been uncovered for the first time by Dr. Qiang Su's team and collaborators.

On October 23, 2024, Dr. Qiang Su's research team and collaborators published a research article titled "Molecular mechanism of IgE-mediated FcεRI activation" in Nature. Immunoglobulin E (IgE) plays a pivotal role in common allergic reactions. This study, for the first time, elucidates the molecular mechanism underlying IgE-mediated immune responses, filling a critical knowledge gap in the activation of the IgE receptor (FcεRI) during allergic reactions and offering important insights for developing new therapeutic strategies for allergic diseases.

Novel Paradigms

Advancing Structural Biology: Cryo-EM at the Forefront

Dr. Nieng Yan's research team has officially launched the CryoSeek Initiative, a pioneering effort to uncover the mysteries of unknown biomacromolecules through the powerful lens of cryo-electron microscopy (cryo-EM). 

On October 9, 2024, Dr. Nieng Yan's research team published a research paper in PNAS titled "CryoSeek: A strategy for bio-entity discovery using cryo-electron microscopy." The study proposed CryoSeek as a novel strategy that employs cryo-electron microscopy (cryo-EM) as a discovery tool, extending the boundaries of human visual capability. By collecting and preparing water samples from the lotus pond at Tsinghua University, the team employed cryo-electron microscopy for imaging, data acquisition, and processing. With the assistance of CryoNet -- an AI-powered software developed by Dr. Fengqiang Zhang's team – they successfully resolved high-resolution 3D structures of two filamentous proteins from previously unknown species, demonstrating the potential of structure-based identification and functional prediction of biological entities entirely through structural analysis.

The team continued to make significant progress and published a follow-up study on January 1, 2025, in the same journal, titled "CryoSeek II: Cryo-EM analysis of glycofibrils from freshwater reveals well-structured glycans coating linear tetrapeptide repeats." By analyzing natural freshwater samples using cryo-electron microscopy, the team discovered highly ordered glycan structures coating linear tetrapeptide fibrils. When several AI-assisted software tools failed to automatically build the atomic model, the team drew on their expertise and meticulous analysis. By identifying a crucial clue—that 3,4-dihydroxyproline is the only residue that can be simultaneously modified by two glycans—they successfully constructed the atomic model of TLP-4a manually. This type of structural discovery lays the groundwork for the development of new methods for glycan structure prediction. The discovery of similar structures -- namely, well-structured glycan coating linear tetrapeptide repeats -- lays the groundwork for the development of novel methods for glycan structure prediction

The above studies demonstrate that CryoSeek, as a research strategy leveraging cryo-EM, enables the discovery of previously unknown biomacromolecules. It opens new paradigms in structural biology and fosters the advancement of interdisciplinary research.

Recent Review

Twin Breakthroughs in Voltage-Gated Ion Channel Studies 

SMART research team has conducted an in-depth, multi-dimensional exploration of the structure and function of voltage-gated ion channels (VGICs), offering new theoretical foundations and novel methodological approaches for the treatment of relevant diseases and the development of targeted therapeutics. 

Dr. Nieng Yan, Dr. Xiaojing Pan, and Dr. Jian Huang Elucidate the Structural and Pharmacological Modulation Mechanisms of VGICs

On August 5, 2024, Dr. Nieng Yan, Dr. Xiaojing Pan, and Dr. Jian Huang published a review article titled "Structural Biology and Molecular Pharmacology of Voltage-Gated Ion Channels" in Nature Reviews Molecular Cell Biology. The article surveys the latest advances in the structural biology of voltage-gated ion channels (VGICs) and provides a detailed analysis of their mechanisms of action. It highlights how drug molecules and toxins modulate VGIC activity, laying the groundwork for rational structure-based drug design and development. The review also discusses emerging progress in structural biology, with particular emphasis on AI-assisted protein structure prediction.

Dr. Nieng Yan's research team proposes a structure-based residue numbering scheme for VGICs and its applications in drug discovery

On August 15, 2024, Dr. Nieng Yan's research team published a review article titled "A versatile residue numbering scheme for Nav and Cav channels" in Cell Chemical Biology. This comprehensive review outlines the latest structural advances in voltage-gated ion channels and elucidates their functional mechanisms. The article highlights representative drug-binding sites in eukaryotic Nav and Cav channels and introduces a structure-based residue numbering scheme centered on the most conserved residues within each functional segment. This scheme enables direct comparison of common disease-causing mutations across different Nav subtypes and facilitates the standardized description of drug-binding sites. The proposed universal numbering framework is expected to enhance understanding of pathogenic mutations and critical drug interaction sites, thereby accelerating drug discovery efforts targeting Nav and Cav channels.

In time we trust, through motion we persevere

In 2025, SMART will harness innovation with unwavering commitment to: 

Constructing Shenzhen BioBay – Forging East Asia' Biopharma Hub

Championing the Healthy China Initiative – Delivering Shenzhen's Strategic Contributions