Biological assays have dramatically improved in recent years due to the increasing use of living cells as "test tubes" for research studies. These cell-based assays have demanded that new technologies be developed for the life sciences in order to fully exploit the potential of designer drugs, stem cell engineering, and genetic medicine. The Allbritton Group is at the forefront of this technology development for biomedical and pharmaceutical research.
Microanalytic Technologies
Traditional biochemical assays have limitations when used for assays in cells obtained from patients; therefore, the Allbritton Group has worked to develop new technologies that address critical needs for biochemical studies within live cells. The laboratory has pioneered advanced tools for analytical chemistry that now make it feasible to perform enzyme assays in individual cells taken directly from patients. In collaboration with colleagues David Lawrence and Marcey Waters in the Department of Chemistry and colleagues in the School of Medicine, the group is developing new chemical compounds that will act to report the abnormal behavior of specific enzymes in blood or biopsy specimens. This cell-by-cell measurement of enzyme activity in patients will have widespread value for individualizing or customizing patient therapy and will provide critical information for physicians using the new generation of molecularly targeted drugs used in the treatment of patients with cancer, autoimmune syndromes, neurodegenerative disorders, and a variety of other diseases.
The Crimmins Group focuses on new methods development for the stereoselective construction of complex biologically active natural products. Most specifically, titanium enolates of acyloxazolidinethiones and acylthiazolidinethiones can be utilized in the enantio- and diastereoselective formation of beta-hydroxy acid derivatives and alpha, beta-hydroxy acid derivatives through chiral auxiliary-controlled aldol additions. All possible diastereomers can be accessed through slight modifications of reaction conditions. These diastereoselective aldol reactions can be applied to the construction of polyketide natural products such as apoptolidin, sorangicin A, irciniastatin A, and iriomoteolide A. Additionally, incorporation of a terminal alkene into the aldehyde and acyloxazolidinethione allows for the ultimate construction of medium ring ethers by means of ring-closing metathesis. Utilization of this strategy recently culminated in the enantioselective synthesis of the complex ladder toxin Brevetoxin A.
Undergraduate proficiency exams will be given on
Monday, August 19, 2013
Follow this link for more information about the exam, beginning at 08:30 am in Venable/Murray Hall G202.
Margaret Radack, an undergraduate chemistry major in the You Group, has been selected to receive the Gertrude Elion Undergraduate Scholarship Award by the North Carolina section of the American Chemical Society. The award is in memory of Gertrude B. Elion, 1988 Nobel Laureate in Medicine, and honors her interest in fostering the research careers of students, and particularly women.
Margaret, who will begin her senior year this fall, is currently doing her summer research program in the You Group, focusing on the development of new strategies to increase the light absorption width of conjugated polymers. Such polymers can more effectively harvest the solar spectrum, with a great potential to increase the current of these polymers based solar cells. Congratulations, Maggie!
Published in JACS, researchers in the Papanikolas and Waters groups, in collaboration with members of the Meyer group at Carolina Chemistry and the Papoian Group at the University of Maryland, describe how solid-phase peptide synthesis has been applied to the preparation of phosphonate-derivatized oligoproline assemblies containing two different RuII polypyridyl chromophores coupled via "click" chemistry.
In water or methanol the assembly adopts the polyproline II (PPII) helical structure, which brings the chromophores into close contact. Excitation of the assembly is followed by rapid, efficient intra-assembly energy transfer to the inner RuII. The oligoproline/click chemistry approach holds great promise for the preparation of interfacial assemblies for energy conversion based on a family of assemblies having controlled compositions and distances between key functional groups.
Work entirely designed, implemented, and interpreted by UNC undergraduates has been published in Biochemistry and is highlighted on the journal web page. Many viruses encode their genetic information in RNA molecules and these RNAs can have complex structures that are essential for efficient replication. The all-undergraduate team developed a model for the genome of the satellite tobacco mosaic virus, which is roughly the "hydrogen atom" of RNA viruses.
The UNC undergraduates discovered that the RNA genome has a complex higher-order structure with three domains, each of which corresponds to an essential viral function. This work is likely to broadly inform our understanding of the role of genome structure in the infectivity and pathogenesis of many RNA viruses, including those that infect humans.
The work was carried out as part of the UNC Undergraduate Transcriptome Project, an NSF-funded program developed in the Weeks Laboratory, designed to help undergraduates explore their potential for independent creativity, to fuel their passion for science, and to be a model for engaging undergraduates in a research university.
Published in Macromolecules, Jason Rochette in the Ashby Group describes how the synthesis of a library of poly(ester urethane)s (PEUs) containing pendant photoresponsive moieties afforded through the incorporation of one of two novel bifunctional monomers resulted in degradable materials with a range of tunable thermal and mechanical properties.
Examination of these materials under physiological conditions displayed tunable degradation with rates faster than PCL-based materials, and initial biocompatibility studies exhibited negligible cytotoxicity for HeLa cells based on results of ATP assay. The ability to tune thermal properties also allowed specific polymer compositions to boast transition temperatures within a range of applicable temperature for thermal shape memory.
Photoresists are light-sensitive resins used in a variety of technological applications. In most applications, however, photoresists are generally used as sacrificial layers or a structural layer that remains on the fabrication substrate. Researchers in the Allbritton Group, as described in the Journal of Micromechanics and Microengineering, have fabricated thin layers of patterned 1002F photoresist released to form a freestanding film. Films of thickness in the range of 4.5–250 µm were patterned with through-holes to a resolution of 5 µm and an aspect ratio of up to 6:1. Photoresist films could be reliably released from the substrate after a 12 h immersion in water. The Young's modulus of a 50 µm-thick film was 1.43 ± 0.20 GPa.
The investigators demonstrated the use of the films as stencils for patterning sputtered metal onto a surface, and these 1002F stencils were used multiple times without deterioration in feature quality. Furthermore, the films provided biocompatible, transparent surfaces of low autofluorescence on which cells could be grown. Culture of cells on a film with an isolated small pore enabled a single cell to be accessed through the underlying channel and loaded with exogenous molecules independently of nearby cells. Thus 1002F photoresist was patterned into thin, flexible, free-standing films that will have numerous applications in the biological and MEMS fields.