Yi Lu
Summer Lab Size: 20
Program Dates: June 1-July 31, 2015 (Dates for 2016 should be similar)

Functional DNA Nanotechnology and Its Application in Biosensing, Bioimaging, and Medicine

Development of highly specific agents for cellular targets is critical for success in biosensing, bioimaging, and targeted drug delivery. Despite recent progress, designing these agents based on a single class of molecules for a broad range of cellular targets with high selectivity remains a significant challenge. Particularly challenging are sensing, imaging, and drug targeting of small molecular targets, for which antibodies have not been very effective. Most processes are on a trial-and-error basis, and we need to develop general strategies to (1) obtain specific agents, (2) improve selectivity of the agents, (3) transform the molecular recognition into either detectable sensing signals or specific drug delivery events, and (4) tune the dynamic range to match the concentration levels of the targets.

We have been able to use a combinatorial method called in vitro selection to obtain functional DNAs (DNAs with specific binding and enzymatic activities, also called aptamers and DNAzymes) that can bind targets of choice strongly and specifically. In addition, we have also used a negative selection strategy to improve the selectivity. By labeling the resulting functional DNA with fluorophore/quencher, gold nanoparticles, quantum dots, and supermagnetic iron oxide nanoparticles, we have developed new classes of fluorescent, colorimetric sensors as well as smart MRI contrast agents for metal ions (such as lead and uranium), organic molecules, and biomolecules. A novel approach of using an inactive variant of functional DNA to tune the detection range of the sensors has also been demonstrated. For even more straightforward field applications, these sensors have been converted into simple "dipstick" tests for qualitative detection. We have also adapted widely available personal glucose meters for quantitative detection of many other targets beyond glucose. Finally, we have used the functional DNA to achieve target-specific drug delivery, and complementary DNA as an antidote to tune the effectiveness of the drugs.

Rational Design of Metalloproteins as Biocatalysts in Alternative Energies

Metalloproteins play critical roles in sustainable energy, such as in photosynthesis, biomass conversion, biofuel cells, and water splitting or oxidation. These proteins cannot be used in practical applications because of cost and stability issues. In addition, although cost-effective and stable, small biomimetic compounds that reproduce either the structure or function of the proteins can be very difficult to make. We have been using small, stable, easy-to-produce, and well-characterized proteins as "ligands" to make biosynthetic models of metalloproteins, such as cytochrome c oxidase and manganese peroxidase. Such biosynthetic inorganic chemistry combines the advantage of cost-effectiveness and stability of small molecules with several structural features in proteins, particularly noncovalent secondary coordination sphere modulations.

In the first example, we have shown that the presence of water as part of the hydrogen-bonding network is necessary to mimic the heme-copper center in cytochrome c oxidase, a terminal oxidase in the conversion of the energy in O2 to proton gradient. In the second example, we have demonstrated the fine-tuning of reduction potentials of azurin—a member of the cupredoxin family that is involved in long-range electron transfers in many important biological processes such as photosynthesis—to span >1 V through careful design of hydrogen-bonding networks around the primary coordination sphere. Both examples demonstrate the importance of noncovalent secondary coordination sphere interactions in making functional models of metalloproteins.

Scientist Profile

HHMI Professor
University of Illinois at Urbana-Champaign
Chemical Biology