LEXINGTON, Ky. (Aug. 29, 2022) — A study led by the University of Kentucky has been selected for funding by the National Science Foundation’s “Biodiversity on a Changing Planet” program, an international, transdisciplinary effort that addresses major challenges related to climate change. The five-year project has been awarded nearly $2.5 million.
This summer, Jim Krupa, UK biology professor, led a course on the evolutionary ecology of the Galápagos archipelago.
“The life on the islands is almost otherworldly,” Krupa said. “The students are absolutely shocked and amazed when they arrive. It’s incredible to see their reactions.”
UK Chemistry Doctoral Student Receives U.S. Department of Energy Stipend By Richard LeComte
LEXINGTON, Ky. – Henry Pruett, a doctoral stud
ent in the Department of Chemistry in the University of Kentucky College of Arts & Sciences, has received a U.S. Department of Energy Office of Graduate Student Research fellowship, which provides a stipend of $3,600 a month.
The University of Kentucky Army ROTC Wildcat Battalion invites you to the Annual Alumni Breakfast on 17 SEP 22 at the Buell Armory hosted by LTC Alan R. Overmyer and LTC (R) Phil Tilly. Followed by the Honoring Heroes UK Football game versus Youngstown State.
Abstract: The biosynthesis of both fatty acids and polyketides involves a common reaction, the iterative carbon-carbon bond formation between acyl-thioesters and malonyl-thioesters. While fatty acids and polyketides are essential to society for a plethorea of reasons, how the underlying carbon-carbon bond forming reactions occur remains an open question. Malonyl-thioesters are akin to biochemical hot-potatoes, because they are prone to hydrolysis and decarboxylation. While these two high-energy reactions are exploited by nature for biosynthetic purpose, they plague the structural biologist. We developed molecules that look like malonyl-thioesters but are much more stable, thus we have chilled the hot-potato. These stable malonyl-thioester analogs have provided us with insight into the catalysis of three enzymes. Our preliminary studies with these malonyl-thioester analogs demonstrate that we will be able to generate insight into fatty acid and polyketide biosynthesis, paving the way for new routes to drugs, agrochemicals and biofuels.
The Yoshimoto research laboratory at UTSA harnesses the power of synthetic chemistry to solve challenging problems relevant to human health.
Artemisinin, one of the topics of the 2015 Nobel Prizes in Medicine, is an endoperoxide-containing sesquiterpenoid plant natural product used to treat malaria. The biosynthesis of the endoperoxide functional group, which gives the natural product its antimalarial activities, has been controversial. Using isotope-labeling strategies, we have elucidated the mechanism of the nonenzymatic endoperoxide forming cascade reaction that converts the precursor, dihydroartemisinic acid, to artemisinin in four steps: (i) first oxygen incorporation, (ii) C-C bond cleavage, (iii) second oxygen incorporation, (iv) and polycyclization to form artemisinin (1,2). Analogs of DHAA have been synthesized to probe endoperoxide formation, which led to the elucidation of the mechanism of the formation of the aromatic ring in serrulatene, an antibiotic plant natural product (3).
Secondly, human cytochrome P450 8B1, the oxysterol-12a-hydroxylase enzyme implicated in bile acid biosynthesis, is a therapeutic target to treat obesity. Preliminary studies involving the synthesis of a rationally designed inhibitor of P450 8B1 through the incorporation of a C12-pyridine in the steroid backbone, will be discussed (4).
1. Varela, K., Arman, H. D., and Yoshimoto, F. K. (2020) Synthesis of [3,3-2H2]-Dihydroartemisinic Acid to Measure the Rate of Nonenzymatic Conversion of Dihydroartemisinic Acid to Artemisinin. J. Nat. Prod. 83, 66-78
2. Varela, K., Arman, H. D., and Yoshimoto, F. K. (2021) Synthesis of [15,15,15-2H3]-Dihydroartemisinic Acid and Isotope Studies Support a Mixed Mechanism in the Endoperoxide Formation to Artemisinin J. Nat. Prod. 84, 1967-1984
3. Varela, K., Al Mahmud, H., Arman, H. D., Martinez, L. R., Wakeman, C. A., and Yoshimoto, F. K. (2022) Autoxidation of a C2-Olefinated Dihydroartemisinic Acid Analogue to Form an Aromatic Ring: Application to Serrulatene Biosynthesis. J. Nat. Prod. 85, 951-962
4. Chung, E., Offei, S. D., Jia, U. A., Estevez, J., Perez, Y., Arman, H. D., and Yoshimoto, F. K. (2022) A synthesis of a rationally designed inhibitor of cytochrome P450 8B1, a therapeutic target to treat obesity. Steroids 178, 108952
Dr. Michele Di Pierro Di Pierro Lab
Abstract:
The human genome is composed of 46 DNA molecules — the chromosomes — with a combined length of about two meters. Chromosomes are stored in the cell nucleus in a very organized fashion that is specific to the cell type and phase of life; this three-dimensional architecture is a key element of transcriptional regulation and its disruption often leads to disease. What is the physical mechanism leading to genome architecture? If the DNA contained in every human cell is identical, where is the blueprint of such architecture stored?
In this talk, I will demonstrate how the architecture of interphase chromosomes is encoded in the one-dimensional sequence of epigenetic markings much as three-dimensional protein structures are determined by their one-dimensional sequence of amino acids. In contrast to the situation for proteins, however, the sequence code provided by the epigenetic marks that decorate the chromatin fiber is not fixed but is dynamically rewritten during cell differentiation, modulating both the three-dimensional structure and gene expression in different cell types.
This idea led to the development of a physical theory for the folding of genomes, which enables predicting the spatial conformation of chromosomes with unprecedented accuracy and specificity. Finally, I will demonstrate how the different energy terms present in our model impact the topology of chromosomes across evolution. Our results open the way for studying functional aspects of genome architecture along the three of life.
Bio:
Michele Di Pierro is Assistant Professor of Physics at Northeastern University and senior investigator of the Center for Theoretical Biological Physics — an NSF Frontier of Physics Center. He studied Condensed Matter Physics at the University of Rome “La Sapienza” and received a PhD in Applied Mathematics from The University of Texas at Austin. Prior to joining Northeastern University, he was the Robert A. Welch Postdoctoral Fellow at Rice University.
His research focuses on the physical processes involved in the translation of genetic information, a branch of biophysics which he refers to as Physical Genetics. His group develops novel theoretical approaches to characterize the structure and function of the genome using the tools of statistical physics, information theory, and computational modeling.
The EGSO stars have aligned...
Halloween Happy Hour
Ethereal Brewing House
Friday, October 28th, 2022
4:00-7:00pm
Raffle for a local Tarot Reading
Prizes for Best Literary Costume, Best Couple's Costumes, and Best Overall Costume
