A world-leading center in single-molecule biomedical research within the Structural Biology Department at St. Jude Children's Research Hospital.
The Single-Molecule Imaging Center (SMC) brings the power of single-molecule spectroscopy techniques to the biomedical research at St. Jude. To fully understand how proteins, nucleic acids and their complexes function, one needs to examine how they move, expand and contract in real time – motions essential to activity – and elucidate how these are modulated by other cellular components.
Single-molecule techniques allow measurements of molecular distances in the order of millionths of millimeters, enabling the visualization of conformational changes underpinning the activities of individual molecules as they perform their functions. By identifying the full diversity of a molecule's dynamic behaviors, which cannot be resolved by bulk measurements, single-molecule approaches have provided unprecedented functional and regulatory insights into complex biological processes, including protein synthesis, viral infection, neurotransmission, and gene expression.
The SMC employs single-molecule fluorescence and FRET (Förster resonance energy transfer) coupled with total internal reflection (TIRF) microscopy and time-correlated single-photon counting (TCSPC) confocal microscopy, to interrogate a wide array of dynamic properties of individual biomolecules in a variety of environmental conditions. The center also develops and implements instrumental innovations and analytical tools, employing state-of-the-art fluorescent probes, molecular engineering methods, and quantitative data analysis pipelines.
The expert staff scientists at the SMC advise and cooperate with scientists from different fields to design and execute experiments, and analyze and interpret data, thereby creating synergies that cross conventional boundaries between disciplines. Our ultimate goal is to leverage single-molecule technologies to boost efforts toward understanding the molecular origins of disease and help finding new cures.
Access: Researchers, inside or outside the Department, can visit the SMC's intranet pages for information on instruments, sample requirements and preparation (including labeling strategy and fluorophores), as well as guidelines for engagement with the Center, data storage and analyses, publication procedures, and policies. Collaborative proposals are reviewed and considered by the SMC staff members, Dr. Blanchard, and the initiating PIs.
Alessandro Borgia obtained his degree in Molecular Biology and completed a PhD in Biochemistry at University of Rome “La Sapienza”, studying thermodynamics and kinetics of protein folding. Sponsored by a fellowship by the Cenci Bolognetti Foundation, he moved to the laboratory of Prof. Jane Clarke at the University of Cambridge (UK), where he used Atomic Force Microscopy to engineer the mechanical stability of human muscle proteins. Following his interests on single-molecule methods and supported by a European Marie-Curie fellowship, Alessandro then joined Prof. Ben Schuler's group at the University of Zurich (Switzerland), where he applied single-molecule Förster resonance energy transfer (FRET) and other fluorescence-based techniques to investigate protein folding and misfolding processes and the properties of unfolded/disordered state of proteins, discovering novel interaction mechanisms between highly charged intrinsically disordered proteins.
Alessandro Borgia, PhD – Director
Structural Biology MS311
St. Jude Children Research Hospital