Recent work from the Ji (Department of Anesthesiology at Duke) and Derbyshire labs has led to the unexpected discovery that artesunate, a front-line antimalarial, confers protection against infection-induced sepsis and pain-like behavior in mice. Artesunate has been used for decades in the clinic, and while its potent anti-plasmodium activity has been widely studied, little is known about its interactions with host cells. While studying the possible role of the human orphan GPCR GPR37, they found that GPR37 agonists may… read more about Derbyshire Lab Making Strides Toward Treating Malaria »
A recent collaborative effort between the Derbyshire lab at Duke and Prof. Jacquin Niles’ lab at the Massachusetts Institute of Technology discovered a mechanism that helps Plasmodium falciparum parasites survive hostile thermal conditions recapitulating malaria fever. The study shows that P. falciparum, the deadliest of the human malaria parasites, uses the lipid PI(3)P and heat shock protein 70 to stabilize the parasite’s digestive vacuole under heat stress. Read more about their discovery of this… read more about Derbyshire Lab Illuminates How Malaria Parasites Withstand Feverish Temperatures »
The Therien lab studied highly conjugated porphyrin arrays and incorporated proquinoidal linkers— small molecules that have closely aligned LUMO energy levels to the parent porphyrins arrays. They found that capping porphyrin arrays with proquinoidal moleculesarray preserves and enhances conjugation, resulting in a red-shifted emission, while also increasing the radiative rate constant, making these systems uniquely good NIR fluorophores. Read about this excellent work by Erin, Dr. Peng Zhang and former Therien lab members… read more about Highly Conjugated NIR-absorbing Fluorophores Display Extraordinary Absolute Fluorescence Quantum Yield Values »
A paper just published by the Beratan Lab resolves a long standing puzzle in molecular bioenergetics. A class of reactions that lies at the core of biological energy conversion - and underpins Mitchell’s Nobel Prize winning chemiosmotic hypothesis - had remained enigmatic for nearly 50 years. Cursory analysis of these reactions suggested that they should “short circuit” and dissipate energy, rather than transduce it. Jon Yuly, a Physics graduate student at Duke, working with Profs. Beratan and Zhang in Chemistry and… read more about One Universal Free-energy Landscape Supports Efficient Electron Bifurcation Reactions »
The Warren Lab has demonstrated a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. In proof-of-principle studies, they compared a variety of commonly available mask types and observed that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Read about Dr. Fischer's findings in a recent issue of Science Advances,… read more about A Box, a Laser, a Lens, and a Cell Phone: Visual Proof that Face Masks Work in the COVID Fight »
Very commonly, molecules don't evolve simply under quantum mechanics-the evolution is interrupted by exchange or reactions. The study of this kind of coherent evolution in dynamic systems is at the forefront of many disciplines, but has been prominent in magnetic resonance for more than 50 years. However, the arguments that led to the theoretical formalism were motivated under incorrect assumptions. The Warren lab has recently reported on a complete re-interrogation of this problem, and has presented a corrected theory that… read more about Warren Lab Completely Reassess the Foundations of Chemical Exchange Models »
Measuring the behavior of single molecules enables the discovery of states and dynamics obscured by bulk measurements. However, molecules in solution rapidly diffuse in three dimensions, precluding long-duration and high-temporal resolution measurement. In a new breakthrough, Dr. Shangguo Hou of the Welsher Lab has developed 3D single-molecule active real-time tracking (3D-SMART), which can “lock-on” to freely diffusing single molecules in solution for up to minutes at a time! This new single molecule tracking can be… read more about Untethering Single Molecule Spectroscopy with 3D-SMART »
The Derbyshire lab is examining biosynthetic gene clusters of bacteria isolated from the gut of Anopheles mosquitoes, the main vector for the transmission of malaria. Through a bioinformatic analysis, iron-binding siderophores were abundant within microbiome bacteria. After testing the metabolites, two siderophores disrupt mosquito reproduction and also inhibit blood and liver forms of the malaria parasite. Overall, this study sets a foundation for new vector control strategies to inhibit the transmission of the… read more about Derbyshire Lab Sets Foundation for Inhibiting Transmission of Malaria Parasite »
New antibacterial strategies are needed to overcome drug resistance in pathogenic bacteria that produce resistance enzymes called metallo-β-lactamases. The Franz lab and graduate student Abbey Jackson recently discovered that their antibacterial prodrug PcephPT is able to inhibit these enzymes. PcephPT, an antibacterial prochelator that releases the metal-binding agent pyrithione (PT) upon cleavage by β-lactamases, inhibits the clinically important metallo-β-lactamase NDM-1 by interacting with the zinc-containing active… read more about Franz Lab Takes Aim at Drug Resistance with Metal Binding Agents »
The structure and dynamics of intracellular water constitute the cornerstone for understanding all aspects of cellular function. However, direct visualization of subcellular solvation heterogeneity has remained elusive. To explore this question, graduate student Xiaoqi Lang of the Welsher Lab has demonstrated a vibrational-shift imaging approach to probe solvation at the microscopic level by combining spectral-focusing hyperspectral stimulated Raman scattering (hsSRS) with an environmentally-sensitive nitrile probe. When… read more about The Shape of (Intracellular) Water »
A recent collaborative effort between the Derbyshire lab at Duke, Benoît Witkowski’s lab at the Pasteur Institute in Cambodia, and Dennis Kyle’s lab at the University of Georgia, Athens revealed that Plasmodium vivax, the leading cause of malaria morbidity, co-opts host aquaporin-3 (AQP3). Human AQP3 is recruited to the host-pathogen interface during the infection of liver and blood cells, including elusive dormant liver stage parasites and ex vivo blood isolates. Chemical inhibition of this protein… read more about Derbyshire Lab Targets Malaria Prevention »
The Beratan Lab, in collaboration with researchers Arizona State University, Pennsylvania State University and the University of California-Davis have studied how electrons flow though water molecules, a process crucial for the energy-generating machinery of living systems. The team discovered that the way that water molecules cluster on solid surfaces enables the molecules to be either strong or weak mediators of electron transfer, depending on their orientation. Read about their findings in Cell Press journal Matter…read more about Beratan Lab and Collaborators Pile Water Chains Like Legos »
A team led by Professors Jiyong Hong and Pei Zhou has reported the molecular structure of LpxH in complex with a sulfonyl piperazine inhibitor and the identification of small molecule LpxH inhibitors with improved activity. These findings will facilitate structure-based ligand design for LpxH and help development of novel antibiotics targeting emerging multidrug-resistant nosocomial Gram-negative pathogens. Read more about their discovery in Proceedings of the National Academy of Sciences, USA, available here.
read more about Small Molecule Inhibitors Target a Key Enzyme in Lipid A Biosynthesis »
Recent work from the Derbyshire lab has led to a comprehensive view of the transcriptional dynamics of infection of liver cells by Plasmodium parasites, the causative agents of malaria. Focusing on the parasite transcriptome, they identified clusters of genes functionally enriched for important liver-stage processes such as interactions with the host cell and redox homeostasis. Moreover, the group identified potential transcriptional factor - binding sites within these clusters, most which have never been… read more about Derbyshire Lab Illuminates the Early Stages of Plasmodium Liver Infection »
Ph.D. student Yangju Lin has reported in J. Am. Chem. Soc. a new mechanoacid that is used to report whether, where, and when potentially damaging mechanical events occur in bulk materials (read here!). The same acid might also be used for self-healing and stress-responsive polymers. Read more in a C&E News Highlight here. We look forward to the upcoming JACS Spotlight highlighting the paper in the near future!
read more about Craig Group Opens Up Acid-generating Materials Response »
The Derbyshire lab has recently published a communication in Chembiochem investigating coculture growth dynamics of bacteria isolated from Anopheles mosquitoes, the main vector for the transmission of malaria. Analysis of growth interactions between a dominant microbiome species, Elizabethkingia anophelis, and other mosquito-associated bacteria reveals that E. anophelis inhibits a Pseudomonas sp. through an antimicrobial-independent mechanism. Further examination identifies a… read more about Derbyshire Lab Investigating Coculture Growth Dynamics of Bacteria Isolated from Anopheles Mosquitoes »
Courtney Johnson of the Welsher lab has developed a new strategy for improving the speed of laser scanning microscopy. The technique, called 3D Fast Acquisition Scan by z-Translating Raster (3D-FASTR), uses an electrically tunable lens (ETL) to generate a reproducible 3D sparse sampling pattern which fully and efficiently scans a volume in the fastest possible time without repeating until the volume is complete. This method has shown a 4-fold improvement in the volumetric imaging rate of live cells. The theory underlying 3D… read more about Welsher Lab Speeds Up Live Cell Imaging »
Dr. Neeraj Patwardhan, Zhengguo (Alex) Cai, and Aline Umuhire Juru of the Hargrove lab have built a diverse compound library based on amiloride, a previously known RNA-targeted scaffold. They used a fluorescent indicator displacement assay to screen the library and quantified the binding profiles of the hit compounds. A cheminformatics study and quantitative modeling elucidated the key factors involved in small molecule recognition for different RNA targets, leading to the successful prediction of a test molecule and the… read more about Hargrove Lab Elucidates Driving Factors of Amilorides Interacting with HIV RNA Targets »
Dr. Lizzie Hunsaker of the Franz lab has discovered that Candida albicans comprehensively remodels handling of transition metals in response to antifungal drug stress. Specifically, they find that treatment with the antifungal drug fluconazole increases the cell’s need for transition metals and regulation of metal homeostasis is crucial for C. albicans to meet these needs. The findings suggest that inducing vulnerabilities in metal handling pathways could be leveraged to optimize the efficacy of existing… read more about Franz lab uncovers adaptation strategies employed by fungal pathogen Candida albicans during drug stress »
The MONET team has collaborated on the publication of an ACS Cent Sci paper detailing a new structurally based representation system that is capable of handling the stochastic nature of polymers. The proposed system hopes to provide a more effective language for communication within the polymer community and increase cohesion between the researchers within the community. Read more about the MONET Team's "BigSMILES: A Structurally-Based Line Notation for Describing Macromolecules" in the ACS publication here and… read more about MONET Team Paves the Way for Polymer Informatics »
Dr. Shangguo Hou of the Welsher lab has developed an adaptive real-time 3D single particle tracking method which can capture the binding events of single viruses to the surface of live cells. The microscope uses an adaptive algorithm which changes tracking parameters to adjust to changes in the motion of the virus particle. This method opens new avenues into probing the first contacts of virions with cells and tissue. Learn more about the new method in the most recent issue of Small, available here.
read more about Welsher Lab Opens New Avenues to Probe Contact of Virions with Cells and Tissue »
The labs of Professors Michael Therien and David Beratan have collaborated to engineer polarized excited states to "U-Turn" electron transfer. Their recent findings demonstrate that oppositely polarized electronically excited states can be employed to steer photoexcited states toward useful, high-energy products. Read more about how their synthesis of a "supermolecule" allows more of the energy harvested from a photon and how this could be a game changing strategy for solar cells in their recent PNAS publication… read more about Therien and Beratan Labs Get Excited About Solar Energy »
A team effort by the Derbyshire lab has led to the identification of human genes and pathways that facilitate the infection of liver cells by Plasmodium parasites, the causative agents of malaria. Their results suggest that this parasite co-opts the vesicular trafficking of its host cell to support its dramatic growth during the liver stage of infection. This work provides insights into the poorly understood interactions between Plasmodium parasites and the host liver cells they invade. Learn more about their… read more about Derbyshire Lab Takes Aim at Human Cell Machinery »
Knowledge of metal-trafficking processes can be leveraged to develop small molecules that help cells regain metal homeostasis for optimal cellular function or conversely that push cells away from homeostasis and into cellular distress. A recently published Viewpoint from Lizzie Hunsaker highlights lessons and opportunities for research in an area rich for therapeutic development at the interface of inorganic chemistry and cellular biology. Read more in the Inorganic Chemistry article available here.
read more about Franz Lab Interfaces Inorganic Chemistry and Cellular Biology while Outside of Metal Comfort Zones »
A team led by Professors Jiyong Hong and Pei Zhou has discovered a small molecule drug that can stop cancer cells from becoming resistant to chemotherapy. The new compound, which was tested in an animal model of melanoma, could serve as a powerful adjuvant to make current chemotherapies more effective. It works by thwarting cancer’s ability to survive, evolve, and adapt to the onslaught of DNA damage wrought by traditional chemotherapy drugs like cisplatin. Read more about their discovery in the June 6 edition of Cell…read more about Small Molecule Drug May Prevent Chemotherapy Resistance »
The Malcolmson lab has demonstrated that conjugated enynes undergo efficient and selective intermolecular 1,4-hydroamination to afford chiral allenes with a variety of primary and secondary aliphatic amines as well as benzophenone imine as an ammonia surrogate. A large number of allenes are obtained in racemic form with an achiral Pd(DPEPhos) catalyst. Through the design and development of a novel PHOX ligand, the group illustrates that highly enantioenriched allenes may be obtained in several cases. A perfluoroaryl… read more about Malcolmson Lab Illustrates Chiral Allene Synthesis by Pd-Catalyzed Amine–Enyne Couplings »
Lizzie Hunsaker of the Franz lab has discovered that modulating copper levels in the growth environment of Candida albicans reduces tolerance of this pathogen to widely prescribed azole antifungal drugs. Their results suggest that, even though these drugs are capable of coordinating transition metal centers, the observed copper-potentiated activity is not due to the formation of a copper complex. Instead, the data point to a broader relationship between Cu homeostasis and azole antifungals, a relationship that the lab… read more about Franz lab discovers relationship between copper levels and drug tolerance in fungal pathogen Candida albicans »
The Malcolmson lab has demonstrated that internal dienes may undergo regio- and enantioselective additions of enolate pronuclephiles. The transformations are promoted by Pd(PHOX) and Bronsted acid co-catalysts and deliver numerous products bearing 1,2-disubstituted olefins and a variety of alkyl groups at the stereogenic carbon. Read more about this research here in Chemical Science.
read more about Malcolmson Lab Develops Enantioselective Alkylations of Enolates with Dienes »