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Department of Biomedical Engineering at Duke University
One of the first biomedical engineering programs in the United States, the Department of Biomedical Engineering at Duke University consistently ranks among the best in the world. As the department has grown, our faculty have continued to pioneer new areas of biomedical engineering, with strengths in tissue engineering, biomaterials, drug delivery, biophotonics and neuroengineering. Duke BME’s ethos reflects the department’s aspiration to advance biomedical engineering to serve society. As we strive towards this goal, we continue to attract outstanding faculty and students who create innovative solutions to the world’s most challenging healthcare problems.
This collection of articles from Nature Research journals is produced with support from Duke University. Duke University retains sole responsibility for the selection of articles.
As the chair of Duke University’s Department of Biomedical Engineering (BME), I am pleased to present this comprehensive Nature Reprint Collection, which showcases the breadth of innovative scholarship in the department over the past decade.
Established in 1967 by Duke University’s schools of medicine and engineering, the Duke Department of Biomedical Engineering (BME) was one of the first of its kind in the United States and consistently ranks among the best in the world.
Inspired by the post-translational modifications of polypeptides widespread in biological systems, the one-pot synthesis of biohybrid materials was engineered within Escherichia coli using a recombinant expression and post-translational lipidation. The fatty-acid-modified elastin-like polypeptides (FAMEs) prepared, which comprise peptide-amphiphile segments prone to self-assembly fused to a thermally responsive elastin-like polypeptide, exhibit temperature-triggered hierarchical assembly.
The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.
It is unclear whether the transfer of plasmids carrying antibiotic resistance genes can explain their persistence when antibiotics are not present. Here, Lopatkin et al. show that conjugal plasmids, even when costly, are indeed transferred at sufficiently high rates to be maintained in the absence of antibiotics.
Cardiomyocytes derived from human induced pluripotent stem cells could be used to generate cardiac tissues for regenerative purposes. Here the authors describe a method to obtain large bioengineered heart tissues showing advanced maturation, functional features and engraftment capacity.
Intestinal type 2 innate lymphoid cells express the neuropeptide receptor NMUR1, which makes them responsive to neuronal neuromedin U, thereby promoting a type 2 cytokine response and accelerated expulsion of the gastro-intestinal nematode Nippostrongylus brasiliensis.
The extracellular matrix protein agrin promotes cardiac regeneration in adult mice after myocardial infarction; it modulates cardiac differentiation and proliferation by interacting with the dystrophin–glycoprotein complex, Yap and ERK-mediated signalling.
Site-specific recombination and CRISPR-Cas9 have been used to generate genetically engineered mouse models of cancer. Here the authors compare sarcomas generated using both systems and see similar genetic and cellular phenotypes, suggesting CRISPR-Cas9 can be used to rapidly generate sarcoma models.
An optimized formulation of glucagon-like peptide-1 recombinantly fused to an elastin-like polypeptide leads to zero-order release kinetics from a subcutaneous depot and to 10 days of glycaemic control in three mouse models of diabetes.
A programmable model of membraneless organelles comprised of intrinsically disordered proteins (IDPs) containing sequences of low complexity has now been developed. The rules governing the assembly of archetypal IDPs into biologically inspired mixed, layered and size-controlled configurations provides a new means for understanding intracellular phase behaviour of IDPs.
Capacitive coupling between tissue and flexible integrated electronics through a sealing dielectric layer facilitates long-term electrophysiology measurements, as demonstrated in ex vivo Langendorff heart models.
Conjugation of exendin-4 — a drug to treat type 2 diabetes — with a poly(ethylene glycol) (PEG)-based brush polymer reduces the conjugate's reactivity towards anti-PEG antibodies and leads to lower blood glucose levels in mice for up to 5 days after a single injection.
Restoring lost excitability of injured tissue is a paramount of regenerative medicine. By using a combined expression of bacterial voltage-gated Na+ channel, Kir2.1, and connexin-43 in non-excitable human fibroblasts, here the authors generate excitable cells that rescue action potential conduction in an in vitromodel of cardiac fibrosis.
Arrays of bioresorbable, highly doped silicon electrodes with multiplexing capabilities are used as electrocorticography sensors to perform in vivo, reliable acute and chronic recordings for up to one month before dissolving in the body.
Antibiotic-mediated selection may promote or suppress conjugation dynamics, dependent on the population structure, physiological status of cells and energy availability.
A detailed study of the effects of dCas9-KRAB-sgRNA complexes on enhancer activity, gene expression and heterochromatin formation shows high efficacy and specificity.
Through a proteomics approach, Qi and colleagues and Long and colleagues identify the sensor of the unfolded protein response IRE1α as an endogenous substrate of the E3 ubiquitin ligase involved in ER-associated degradation, Hrd1.
The encapsulation of a drug into nanoparticles can be a useful way control and improve its efficacy. Here, the authors conjugate paclitaxel to recombinant chimeric polypeptides that self-assemble into therapeutic nanoparticles that outperform Abraxane in murine tumour models.
Quantification of single-cell growth over long periods of time in E. coli shows transient oscillations in cell size, with periods stretching across more than ten generations; a noisy negative feedback on cell-size control is proposed in which cells with a small initial size tend to divide later than cells with a large initial size with implications for the genetic and physiological processes required.
Duchenne muscular dystrophy is caused by mutations in the dystrophin gene. Here, Ousterout et al. use multiplexed CRISPR/Cas9 genome editing to excise a large portion of the gene that carries over 60% of known dystrophin mutations. They show that this excision restores dystrophin expression in patient-derived cells.
Modification of the CRISPR/Cas9 genome editing system by the addition of the light inducible proteins CRY2 and CIBI1 enables blue light–mediated transcription of endogenous genes in mammalian cells.
The authors use developmental changes in chromatin accessibility to identify thousands of enhancer elements that are active at different postnatal developmental stages in granule neurons of the cerebellum. Zic transcription factors were found to promote gene expression patterns key for neuronal maturation by binding to late-acting enhancer elements.
The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al.provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.
This Technical Report describes new methods of transcranial magnetic stimulation (TMS) in non-human primates. By combining single neuron recording with a modified TMS coil with focused stimulation in alert macaques, the authors show that this method can reduce stimulation artifact and allow investigation into the neuronal mechanisms of TMS.
Synthetic transcription factors based on the RNA-guided CRISPR-Cas9 system are used to activate specific endogenous genes in human cells. Also online, Joung and colleagues report similar developments at two other loci.
The combination of several TALE-TFs that bind the same gene promoter at different positions induces high and tunable activation, even in heterochromatic genes, and offers the promise of engineering complex synthetic gene expression systems.
Randomly adsorbing chemically synthesized silver nanocubes, each of which is the optical analogue of a grounded patch antenna, onto a nanoscale-thick polymer spacer layer on a gold film results in a metamaterial surface with a reflectance spectrum that can be tailored by varying the geometry.
Using a new form of spectroscopic optical coherence tomography, researchers demonstrate three-dimensional molecular imaging of both endogenous and exogenous chromophores with high spectral fidelity. This scheme has significant implications for a range of biomedical applications, including ophthalmology, early cancer detection and understanding fundamental disease mechanisms such as hypoxia and angiogenesis.
Patch-clamp recordings are used to study the function of ion channels, but the method does not allow the assessment of tissue-level function. Kirkton and Bursac introduce a biosynthetic system for the study of channel activity and electrical conduction, facilitating studies of ion channel function.
High-throughput synthesis of long DNA molecules would open up new experimental paradigms in synthetic biology and functional genomics. Quan et al. take a step toward this goal by integrating oligonucleotide synthesis, amplification and gene assembly on a single microarray, and apply the technology to optimization of protein translation in a heterologous host.
A one-pot, high-throughput method for the recombinant polymerization of monomer DNA sequences is reported. The method enables the rapid synthesis of diverse libraries of artificial repetitive polypeptides, exemplified by the isolation of protease-responsive polymers and a family of polypeptides with reversible thermally responsive behaviour.
In an effort to develop safer therapeutic agents and to limit unintended side effects, Sabah Oney and her colleagues have designed a set of antidote molecules for a series of aptamers exhibiting anticoagulant activities. These so-called universal antidotes are shown to sequester circulating aptamers and reverse their activity, irrespective of the primary sequence and folded structure of the aptamer.
When artificial polypeptides are conjugated to a variety of hydrophobic molecules such as chemotherapeutics, the resulting molecules spontaneously self-assemble into nanoparticles. Delivering the chemotherapeutics to a murine cancer model, the nanoparticles have a fourfold higher maximum tolerated dose than the free drug, and induce nearly complete tumour regression after a single dose.