Biomedical Engineering REU
Each summer, the Department of Biomedical Engineering at Duke University provides a Research Experience for Undergraduate students (REU) and hosts undergraduates from around the country in its research laboratories. The REU students will work with a faculty member and their research group to tackle an innovative research project.
Students admitted to the program will receive a competitive research stipend which includes:
- 9 weeks housing on Duke’s campus
- $4,500 stipend
- Up to $400 towards travel costs
All applicants must be United States citizens or permanent residents. The program is designed for student who are juniors during the internship period, but exceptional sophomores will also be considered. Students do not have to be majoring in biomedical engineering.
Application deadline: February
Selected students should expect to hear of their acceptance to the program by April 1st. Student participants will be on site from late May to late July.
Previous Research Opportunities
The following are examples of projects offered in previous years.
Nanoparticle-Film Plasmon Ruler
We have shown that the plasmonic response from film-coupled nanoparticles –composed of a nanoparticle separated from a gold film– undergo drastic color shifts in their localized surface plasmon resonances as the NP-film gap distance changes. Both the spectral and polarization responses from film-coupled NPs can be used as extremely sensitive and localized sensors of distance between the NPs and the nearby film. Additionally, nanoscale gaps created between NPs and film represent tightly confined ‘hot spots’ where electromagnetic fields are enhanced by many orders of magnitude. We have shown that these hot spots can be used to stimulate such low-probability events as surface enhanced resonant Raman scattering from molecules located within the gap regions between NPs and film. We have demonstrated the ability to make high throughput NP-film ‘plamonic ruler’ measurements on a chip by characterizing the plasmonic response from ensembles of NPs near film with a single, quick spectroscopic measurement. We have also demonstrated the ability to make these fast plasmonic ruler measurements in real time, on-the-fly as the NP-film separation distance is perturbed by external stimuli. We are currently developing ways to incorporate these high-throughput plasmonic ruler measurements into biosensing devices.
Sortase: a New Tool for Biotechnology and Materials Science
Fusion proteins are attractive for therapeutic protein purification because the properties of the fusion tag provide a general mechanism for purifying a protein of interest. However, removal of the purification tag from the target protein by proteolytic digestion generates a mixture that requires additional time-consuming and expensive chromatographic separation steps. We are using the Staphylococcus aureus transpeptidase sortase A to cleave ELP fusion proteins and to install small molecule moieties of interest at the cleavage site. Coupling sortase A and target proteins to ELPs enables simple purification of the fusion proteins by inverse transition cycling (ITC), a method that we have previously developed that allows purification of ELP fusion proteins by exploiting the environmentally triggered soluble-insoluble transition of ELP fusion proteins. Using ITC, the target protein can be purified from the cleavage reaction products to >95% purity by a single centrifugation step above the ELP's transition temperature. Subsequent cleavage fp the target-protein-ELp fusion and another round of ITC allows isolation of pure target. Sortase-mediated purification has been successfully applied for a variety of target proteins in two reaction formats: single-fusion (in which the enzyme and target protein are on separate ELPs) and double-fusion (in which the enzyme and target are expressed on the same ELP). The single fusion approach is also interesting because it enables purification to be combined with site specific labeling of the ELP with imaging agents, drugs, haptens or other moieties of interest.
Attachment Triggered Self-Assembly of Drugs into Nanoparticles
We have explored the capacity of ELPs to self-assemble into nanostructures in response to a range of stimuli. In one example, we designed a chimeric polypeptide that consists of two segments: (VPGXG)n repeats followed by a short (GGY)n segment, and showed that attachment of multiple copies of a hydrophobic molecule at the Y position can impart sufficient amphiphilicity to the polypeptide and thereby drive its self-assembly into near-monodisperse nanoparticles with the attached hydrophobic small molecule embedded in the core of the nanoparticle. This is an interesting finding, because it appears that any molecule with a hydrophobicity that is greater than a threshold value appears to drive attachment-triggered self-assembly of the chimeric polypeptide into a nanoparticle. Because many cancer chemotherapeutics are insoluble hydrophobic small molecules with poor bioavailability, this approach of attachment-triggered encapsulation of small hydrophobic molecules into soluble nanoparticles has great utility to increase the solubility, plasma-half-life and tumor accumulation of cancer chemotherapeutics.
Determining Biophysical Mechanisms of Mechanotransduction
As the heart pumps, blood flows and exerts forces on the cells of the vasculature. These forces are critical to normal vascular cell behavior and are important factors in diseases like atherosclerosis and hypertension. However the biophysical processes by which mechanical signals (i.e. force and tension) are converted into biochemical signals interpretable by cells are not well understood. Often cells respond to mechanical signals from the environment by altering their structure. This is largely mediated by force-induced changes in protein dynamics, but the underlying mechanisms are unknown. Current projects include identifying the biophysical mechanisms mediating the force-based regulation of focal adhesions and cell-cell contacts, the structures that mediate the mechanical linkages between the extracellular environment and other cells respectively. This work will provide molecular insight into the force-sensing abilities of vascular smooth muscle cells, which mediate the myogenic response and are important in the development of atherosclerotic lesions.
Quantifying Neural and Behavioral Effects of Deep Brain Stimulation
Our long-term goal is to understand the mechanisms of deep brain stimulation (DBS) – a brain pacemaker used to treat the symptoms of neurological disorders and diseases – and use this knowledge to develop novel methods of stimulation that improve efficacy and decrease side effects. We employ computational models, preclinical experiments in animal models, and clinical experiments in humans to study the effects of DBS in Parkinson’s disease.
The purpose of this project is to quantify the effects of the temporal pattern of DBS on the symptoms of Parkinson’s disease in preclinical experiments using quantitative behavioral evaluations, including gait analysis. These results will be used to establish a correlation between changes in the rate and pattern of neural activity and changes in symptoms thereby providing insight into the mechanisms of action of DBS.
Characterization of Peripheral Blood Endothelial Progenitor Cells for Use in Prosthetic Vascular Grafts
Synthetic grafts made out of ePTFE or Dacron have been looked to for a possible replacement of autologous vessels. However, currently synthetic grafts are limited to vessels with an internal diameter larger than 6 mm due to the thrombogenicity of the material Investigators have attempted to improve the performance of these materials for small diameter applications by coating the lumen with endothelial cells, and successful seeding of endothelial cells has been shown to improve the long-term patency of these grafts. Still, major technical hurtles include finding a relevant autologous cell sources and improving the attachment of endothelial cells to prosthetic grafts.
This project focuses on isolating a type of high proliferation potential endothelial cells that are found in an individual's circulating blood, called endothelial progenitor cells (EPCs). We are currently attempting to determine whether EPCs represent a viable and easily isolated autologous cell source for the seeding onto synthetic vascular grants. The strength of adhesion and the antithrombotic properties of the EPCs on synthetic graft materials will be determined through in vitro assays. Gene therapy will be used to regulate the expression of antithrombotic molecules. Seeded grafts will eventually be tested in animal models. This project involves cell culture, gene expression analysis, and phase/fluorescent microscopy.