Rising Stars Colloquium: Lam-Kiu Fong

Molecular forces that define function in biological systems

Abstract: Biomolecular assembly underlies many biological processes from DNA replication to cell signaling and can become dysregulated in disease. Additionally, biomedical nanomaterials often rely on biomolecular assembly to effectively interface with biological systems. Understanding the thermodynamic forces that drive the assembly of biological molecules is therefore key to understanding disease and improving the design of nanomedicines. In this seminar I will present a combination of experimental and computational approaches to understand how multiple weak, noncovalent interactions drive assembly in biological systems. I will focus my presentation on two systems: DNA-functionalized nanoparticles and multi-component protein receptors. First, DNA-functionalized nanoparticles have been used extensively for diagnostic and therapeutic applications, but the enhanced thermodynamic stability of the DNA duplex when anchored to a nanoparticle surface was poorly understood. My work determined that DNA hybridization on the nanoparticle surface is enthalpically enhanced relative to linear DNA, because structural confinement prevents it from adopting conformationally unfavorable states. This finding both advances fundamental knowledge of DNA hybridization at interfaces and improves the design of DNA-functionalized nanoparticles. Second, multi-component immune receptors that separate ligand recognition and intracellular signaling into a primarily extracellular protein subunit and a primarily intracellular protein subunit respectively, assemble through the interaction between polar residues in the cell membrane. Little was known about what factors enable stable arrangement of these polar residues in the nonpolar membrane environment. By elucidating the molecular level factors that drive assembly, my work explained promiscuous pairing in this class of receptors and furthered our understanding of immune cell function. The ability to elucidate the molecular-level interactions that drive assembly and dictate function in biological systems is essential to understanding biological processes that cause disease, developing novel therapeutics, and designing next-generation biomaterials.

Bio: Lam-Kiu began her research journey as an undergraduate under the supervision of Paul Alivisatos at UC Berkley where she studied how defect structure and chemical composition regulate optoelectronic response in semiconductor nanomaterials. She then went on to complete a Ph. D. in chemistry under the supervision of Chad Mirkin and George Schatz at Northwestern University. Her thesis, “Uncovering the Origins of the Binding Properties of Spherical Nucleic Acids”, advanced fundamental knowledge of DNA binding thermodynamics and nanoparticle synthesis, and specifically addressed limitations to the construction and implementation of DNA-nanoparticle conjugates. Now, as a postdoctoral scholar under the supervision of Bill DeGrado at UCSF, Lam-Kiu is working to understand the molecular determinants of immune receptor assembly and specificity. Lam-Kiu’s work has been funded by the NSF-GRFP, the NIH IRACDA postdoctoral fellowship, the Ford Foundation postdoctoral fellowship and most recently the UC President’s postdoctoral fellowship. Lam-Kiu is passionate about mentorship of students in both the lab and the classroom.