Soma Dhakal Defended his PhD and Joining University of Michigan Ann Arbor for Postdoctoral Position

Nepachem likes to Congratulate Dr. Soma Nath Dhakal for successfully defending doctoral dissertation. He is going to start a postdoctoral position at Walter Lab, University of Michigan Ann Arbor next month. Please refer to the following texts for the brief overview of his research accomplishments.

MECHANICAL STABILITY EVALUATION OF I-MOTIF AND G-QUADRUPLEX STRUCTURES UNDER DIVERSE CIRCUMSTANCES

‘ILPR (Insulin Linked Polymorphic Region) is a promoter region located upstream of the human insulin gene.  This region facilitates the transcription and hence regulates the production of insulin, a hormone responsible for the metabolism of glucose.  When the control of insulin level fails, it leads to insulin related health problems such as diabetes.  One of the scenarios that influence the transcription of the insulin gene can be the formation of secondary structures in the promoter.  Due to the prevalence of the guanine (G)- and cytosine (C)-rich repeats in the ILPR promoter, it is likely to form unusual structures such as G-quadruplex and i-motif in the respective strands. 

G-quadruplex and i-motif structures are the most widely known four-stranded nucleic acid structures which are shown/proposed to alter gene regulation.  Although there is significant understanding on the folding topologies of G-quadruplex and i-motif structures, their mechanical stability which determines the interaction with motor proteins, such as DNA/RNA polymerases, are poorly studied. Using laser tweezers based single-molecule study; we investigated, for the first time, the mechanical stability of an i-motif structure in the predominant variant of human ILPR.  Similarly, using ensemble and single-molecule approaches, we show that a dsDNA fragment in ILPR can fold into G-quadruplex or i-motif structure under specific conditions. Under a condition that favors the formation of both G-quadruplex and i-motif, we provide compelling evidence that only one species is present in each dsDNA.  We propose that G-quadruplex and i-motif are mutually exclusive in human ILPR.  Due to the fact that these two species have an unfolding force comparable to the stall force of RNA polymerase, these DNA structures may play significant biological rules in the expression of human insulin inside cells.’

Below are some selected publications: 

Dhakal et al., Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions, Nucleic Acids Research, 2013, Accepted

Dhakal et al., Intramolecular folding in human ILPR fragment with three C-rich repeats PLoS ONE 7(6): e39271. doi:10.1371/journal.pone.0039271

Dhakal et al., G-quadruplex and i-motif are mutually exclusive in double stranded ILPR DNA, Biophysical Journal, 102, 2575–2584

Dhakal et al., Formation of human ILPR G-quadruplex in dsDNA, International Review of Biophysical Chemistry, 2011, 2, N. 6.

Dhakal et al., Coexistence of an ILPR i-motif and a partially folded structure with comparable mechanical stability revealed at the single molecular level, J. Am. Chem. Soc. 2010, 132, 8991–8997  

Book Chapter:

Dhakal, S.; Mao, H.; Rajendran, A.; Endo, M.; Sugiyama, H., Eds: Spindler L, Fritzsche W., “G-quadruplex Nanostructures Probed at The Single Molecular Level By Force-Based Methods” in Guanine quartets: Structure and Application, RSC Publishing, 2013, 73-85.

Hahn Lab Univ of North Carolina-Chapel Hill Postdoc Positions

Departments of Pharmacology, Medicinal Chemistry,
and Lineberger Cancer Center

 

We are seeking postdoctoral fellows to develop and apply novel approaches for in vivo manipulation and imaging of signaling. We are a multidisciplinary team using protein engineering, organic chemistry, and novel microscopy techniques to study the dynamics of signaling networks in living cells and animals.  We seek postdoctoral fellows to design novel biosensors, molecules for photomanipulation of protein activity, and engineered allosteric activation of signaling pathways. Other positions focus on the flow of information through signaling networks controlled by spatio-temporal dynamics, and involve interactions with groups developing models of network behavior and computational tools to understand and model imaging data. See the Hahn lab web site for more information about our work and the exciting collaborative environment at UNC. (hahnlab.com). See also Gulyani et al. Nature Chem. Bio 7:437 p437; Karginov et al. Nature Biotech 28(7) p743; Yoo et al. Developmental Cell 18 p226; Wu et al. Nature 461 p104; and Machacek et al Nature 461 p99.

Chemical Biology. We seek postdoctoral fellows experienced  in the design and execution of complex multi-step organic syntheses. This position offers the opportunity for an organic chemist to move into a new area of research, focusing on projects that combine organic synthesis and molecular biology to develop new tools for the imaging and manipulation of signaling pathways in vivo. There will be multiple opportunities to apply your new tools in biological studies.

Biophysics and imaging. We are developing novel biophysical techniques based on lifetime imaging, single molecule imaging and correlation microscopy to study signaling dynamics in living cells. These projects will require a background in mathematics, physics or engineering, and ideally an understanding of microscopes, lasers, and/or programming for microscope automation.  This is a collaboration with Enrico Gratton of the Laboratory of Fluorescence Dynamics (http://www.lfd.uci.edu/).

GEF- GTPase signaling networks. These positions are for postdocs interested in protein engineering and/or the spatio-temporal dynamics of signaling networks.  Projects focus on a) developing novel biosensor approaches for signaling upstream and downstream of GTPases b) methods for control of such molecules in vivo, and/or c) use of these tools to dissect the spatio-temporal dynamics of signaling networks controlling cell polarization and trans-endothelial migration. We will interact closely with Dr. Gaudenz Danuser developing network models and computational approaches to derive information re the spatio-temporal dynamics of signaling from imaging data (http://lccb.hms.harvard.edu/), and with Drs. Keith Burridge (http://www.med.unc.edu/cellbiophysio/faculty/burridge) and with John Sondek of UNC (http://www.med.unc.edu/pharm/sondeklab/) , who study the biology and structural biology of GEFs and GTPases. Applications in vivo will be carried out with Dr. Anna Huttenlocher, examining TEM in zebrafish models (http://medmicro.wisc.edu/people_faculty.php).

To apply, please send a CV to Klaus Hahn at khahn@med.unc.edu.

£250 prize for schools electrochemistry challenge

The RSC's Electrochemistry Group is inviting students to enter a competition to design a battery and win up to £250.

The competition asks students 'Imagine you had a power cut at home - what could you use to produce some power?' The group are looking for the most imaginative solution that uses materials found in the home and garden.

A separate set of prizes is available to the best entry of a cartoon or illustration that demonstrates an electrochemical principle. Again, the judges are looking for creativity and entrants are asked to 'think different!'

More information can be found on the RSC Electrochemistry Group website. The deadline for entries is 15 December 2012.

more here: http://www.rsc.org/Membership/Networking/InterestGroups/Electrochemistry/electrochemistry-challenges.asp

Congratulations to Dr. Kattel

Krishna Kattel (Dr. Kattel now) completed his PhD from Kyungpook National University, Korea.

Congratulations Dr. Kattel. 

His thesis title was: 

"Synthesis, Characterization, In Vitro and In Vivo Studies of Lanthanide Oxide/Hydroxide Nanostructures for Magnetic Resonance Imaging (MRI) Contrast Agent and Fluroscence Imaging (FI) Agent."

The size, composition, and shape of the nanoparticles are tuned by controlling reaction conditions. These nanoparticles are made dispersible in various media through proper surface modifications. The effects of particle size, shape, composition, and interparticle spacing on physical and chemical properties of the nanostructures are addressed by my research. I accomplished the synthesis of a series of biocompatible multifunctional magnetic nanoparticles for highly efficient diagnostic and therapeutic applications. In addition, I synthesized various paramagnetic lanthanide oxide nanoparticles for advanced T1 and T2 MRI contrast agents. I demonstrated the applicability of antibody conjugated iron oxide nanoparticles for cancer cell separation in buffer and IO-Ab nanoparticles to capture cancer cells without pre-treatment process.

As an extension of my research, I am planning to do further research on gold nanoparticles for a wide range of biological studies. Through precise control over the particle morphology and surface modification, I plan to design and create gold nanostructures that can be used for applications such as bio-sensing and therapeutics.

More on Dr. Kattel's can be found on his publications.
1) Kattel, K.; Park, J. Y.; Xu et al. “A Facile Synthesis, In Vitro and In Vivo MR Studies of D-glucuronic Acid Coated Ultrasmall Ln2O3 (Ln = Eu, Gd, Dy, Ho and Er) Nanoparticles as a New potential MRI Contrast Agent.” ACS Applied Materials and Interfaces, 2011, 3, 3325-3334. (IF:4.5)

2) Kattel, K. et al.; “Water–Soluble Ultrasmall Eu2O3 Nanoparticles as a Fluorescent Imaging (FI) Agent: In Vitro and In Vivo Studies.” Colloids and Interfaces A: Physiochemical and Engineering Aspects 2012, 394, 85-91. (IF: 2.3).

3) Kattel, K.; Park, J. Y.; Xu, W.; Kim, H. G.; Lee, E. J.;et al. “Paramagnetic Dysprosium Oxide Nanoparticles and Dysprosium Hydroxide Nanorods as new T2 MRI contrast agent.” Biomaterials 2012, 33, 3254-3261. (IF: 7.88).

4) Xu, W.*; Kattel, K.*; Park, J. Y.*; Chang, Y.; Kim, T. J.; Lee, G. H. “Paramagnetic Nanoparticle T1 and T2 MRI Contrast Agents.” Phys. Chem. Chem. Phys. 2012, 14, 12687-12700. [*authors have equal contributions]. (IF. 3.6)
5) Kattel. K. et al. “Surface Coated Eu(OH)3 Nanorods: A Facile Synthesis, Characterization, MR Relaxivities and In Vitro Cytotoxicity.” Journal of Nanoscience and Nanotechnology. (Just accepted).

Our congratulation to Dr. Anant Marahatta

Anant Marahatta successfully defended his PhD dissertation this month (2012, November) at Tohoku University Sendai, Japan. We would like to congratulate him for his achievement. 

 

His Ph.D. research work is mainly concentrated on the “Theoretical investigation of the structures and dynamics of the crystalline molecular gyroscopes”. His work is regarded as a complementary theoretical study that aimed to characterize the experimentally synthesized crystalline molecular gyroscopes (It is a compliment from the ACS reviewers). He computed series of quantum chemistry calculations by applying Gaussian-03 and density-functional-based tight-binding program (DFTB+) packages. Here is a short description   of his research work.

 

The phenylene-bridged macrocages whose interior rotator (phenylene) is protected by an exterior framework (stator) are found to be structurally analogous with the macroscopic gyroscope and expected to have many several useful collective effects and properties in the crystal such as dichorism and birefringence. Recently, an X−ray crystallography of the gyroscope like molecule having a phenylene rotator encased in three long siloxaalkane spokes was reported by Prof. W. Setaka and his group. They observed the phenylene rotator at three stable positions around the molecular axis, suggesting the molecule demonstrates functions as a molecular gyroscope in crystal. The rotational dynamics and the underlying mechanisms of such novel molecular gyroscope were not revealed. I am the first to carry out series of quantum chemistry calculations for theoretically investigating its crystal structures and the rotational dynamics. Another objective of my research is finding computationally cheap yet decent theoretical method that can characterize the experimentally synthesized crystalline molecular Gyroscope.

 

The most important conclusion of this research work is that in the presence of highly efficient encapsulating frame around the rotating segment, the rotational dynamics of crystalline molecular gyroscopes can be dramatically improved with an extremely low activation barrier. It is very essential to realize the rotationally free molecular machines. I am able to reveal the microscopic mechanisms of rotations with the help of reasonably simple theoretical methods. It will be highly beneficial for the development of nanoscale devices based on assemblies of molecular gyroscopes.

 

He has started a post-doctoral position at the same University in Japan. We wish him a successful career ahead.

For detail, you can go through his research paper:

http://pubs.acs.org/doi/abs/10.1021/jp308974j

Dr. Pandey moving to PENNSTATE for post-doctoral position

Binod Pandey successfully defended his PhD dissertation this month at University of Missouri – Saint Louis, US. We would like to congratulate him for his achievement.

Here is a short description of his PhD research.

Gold nano-structures are at the center of nanoscience and nanotechnology. Nanoporous gold is a gold nanostructure with pores and ligaments in the nm dimensions. Size and topography of these pores and ligaments can be compared to the dimensions of the microdomains of the membrane. Highly increased surface to volume ration of the nanoporous gold makes it an attractive substrate for protein immobilization and assay development. My study involved utilization of nanoporous gold for the development of electrochemical immunoasays for the cancer biomarkers such as prostate specific antigen (biomarker for prostate cancer) and carcinoembryonic antigen (biomarker for colorectal cancer). Another aspect of the study involved development of electrochemical techniques for the study of carbohydrate lectin interactions on the nanoporous gold surface as an alternate and close mimic of the cell surface for carbohydrate presentation, and as a model for carbohydrate protein interaction studies. Electrochemical lectin assays were also developed for the high throughput screening of the glycan targets in glycoproteins, glycoconjugates and cell surface carbohydrates.

His publications can be viewed at google.scholar site. 

http://scholar.google.com/citations?user=k8_W3EQAAAAJ&hl=en

After his PhD, Dr. Pandey will be joining Benkovic lab at PENNSTATE as a post-doctoral research associate. 

Best wishes from our side Dr. Pandey.

2012 Nobel Prize in Chemistry goes to Robert and Brian

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An X-ray crystal structure depicts the ß2 adrenergic receptor (green) with its G protein, a heterotrimer called Gs (yellow, blue, and purple). The complex is stabilized by a llama antibody (red) and the enzyme T4 lysozyme (magenta).

Credit: Nature

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Lefkowitz

Credit: Stewart Waller/PR Newswire/HHMI

Robert J. Lefkowitz, 69, and Brian K. Kobilka, 57, will take home this year’s Nobel Prize in Chemistry for unraveling the molecular workings of G-protein-coupled receptors (GPCRs). The receptors are a family of proteins that transmit critical biological messages for functions such as vision, smell, taste, and neurotransmission.

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Kobilka

Credit: Stanford U

Lefkowitz and Kobilka’s discoveries also laid the foundation for aflurry of structures of GPCRs solved over the past five years, the Nobel committee said at an Oct. 10 press conference. Those structures explain at atomic-level detail how the receptors, which always wind back and forth seven times through cell membranes, transmit messages.

GPCRs “are crucially positioned to regulate almost every known physiological process in humans,” Lefkowitz, a Howard Hughes Medical Institute investigator based at Duke University Medical Center, said by phone at the press conference. For decades, researchers knew that hormones such as adrenaline outside cells led to changes inside cells. But the exact nature of this chemical signaling was a mystery. Lefkowitz first traced this signaling with radioactive blocking agents. Eventually, his team managed to pluck GPCRs—including the receptor for adrenaline, the β-adrenergic receptor—out of the tissues where they had always been studied.

Kobilka, now at Stanford University School of Medicine, was a postdoc in Lefkowitz’ lab in the 1980s, when the lab was hunting for the gene encoding the β-adrenergic receptor. When Kobilka finally isolated the gene, he realized the receptor comprised seven helices, just like rhodopsin, which resides in the retina and responds to light. The Lefkowitz team realized that a large family of seven-helix receptors must exist. “Lefkowitz and Kobilka have helped us understand the molecular details of cellular signaling,” says American Chemical Society President Bassam Z. Shakhashiri. “It is helping chemists create new medicines that will benefit society.”

GPCRs are targets for as many as 50% of prescription medicines on the market, but many of those drugs, such as beta-blockers, date to long before the prizewinning discoveries. “Chemists made early GPCR drugs by just making molecules related to natural hormones or neurotransmitters,” says Fiona H. Marshall, chief scientific officer of Heptares Therapeutics, a firm that specializes in GPCR drug discovery. Lefkowitz and Kobilka’s work allows medicinal chemists to understand better the proteins they are targeting as they go about designing new drugs, she adds. Although the Nobel committee pointed to Kobilka’s more recent research achievements, including the first X-ray crystal structure of a GPCR bound to its signaling partner, “this Nobel Prize is not just about the GPCR structure,” Marshall says. “That was the icing on the cake at the end.”

Lefkowitz and Kobilka will split the $1.2 million prize, which Lefkowitz said he didn’t anticipate. “I can assure you I did not go to sleep last night waiting for this call.” His original plan for the day, he said, included getting a haircut.

 

Chemical & Engineering News

ISSN 0009-2347

Copyright © 2012 American Chemical Society

http://cen.acs.org/articles/90/web/2012/10/Robert-Lefkowitz-Brian-Kobilka-Share.html