Lab News
Awards for DDTLAB members. Congratulations to the following lab members for awards in 2012:
Mike Autry
- Best Talk, Iowa State University Postdoc Day (2011)
- Postdoc Mentor Award, HHMI-CBS (2012)
John Rubin
- Matriculating into Med School (Fall 2012)
Nick DesLauriers
- HHMI-CBS Undergraduate Research Award (Spring 2012)
- UMN Undergraduate Research Award aka UROP (Summer 2012)
2012: Christine Karim, DDTLAB collaborator and Research Associate Professor, is featured in the Biophysical Society Newsletter in April, 2012. In Biophysicist in Profile, Christine's interesting life and research career are described.
2012: Ava Yun Lin, MD/PhD student who will defend her thesis in June has been awarded the Milne-Brandenburg Award for the outstanding PhD thesis in the Medical School. In the past year, Ava has recently published three papers on her research on the molecular biophysics of muscular dystrophy, in PNAS and J Mol Biol. (Lin et al., 2011, Henderson et al., 2011, Lin et al., 2012). Her discoveries have initiated a new era in the muscular dystrophy field, in which molecular biophysics informs strategies for therapeutic advances in treating the most devastating muscle disease – Duchenne muscular dystrophy.
2011: DDT has received a MERIT (Method to Extend Research In Time) Award from NIH for his proposal, Site-Directed Oxidative Modification of Muscle Protein Structural Dynamics (from NIA, National Institute of Aging). Instead of the standard 5-year award, this grant will be renewed (almost) automatically for a period of 10 years. This is the highest award an investigator can receive based on a R01 research grant; indeed, it has been renumbered as an R37 grant. This is the second time DDT has received a MERIT award. From 1993-2003, he received MERIT from NIAMS for "Molecular Dynamics of Muscle Contraction."
2011: Another honor for Michel! Dr. Lennane Michel Espinoza-Fonseca, who was recently awarded the National Youth Prize of Mexico (see below), has now been awarded the title of National Researcher (Investigador Nacional) by the Mexican Government. This is a prestigious award that recognizes Michel's outstanding scientific productivity and international leadership in his field.
2011: Biophysical Assault on Heart Failure - several developments have combined to inspire the DDTLAB to redirect its efforts in the direction of therapeutic development for heart failure, using the principles of and technologies of structural biophysics that have been pioneered in this lab.
High-performance time-resolved fluorescence (HPTRF)(Muretta et al., 2010). This instrument, (constructed in collaboration with Fluorescence Innovations, Inc.) uses direct waveform recording to acquire a high-quality sub-nanosecond time-resolved fluorescence waveform every 0.1 ms, which is a factor of 100,000 times faster than in current commercial instruments. Time resolution increases the precision of fluorescence detection by an order of magnitude, and the time-resolved fluorescence waveform is rich in information, especially when it corresponds to FRET, where it provides direct and independent information about structural and thermodynamic parameters of the system. We have applied this to resolve structural states in the SERCA-PLB system (Lockamy et al., 2011), myosin light chain domain (Kast et al., 2010), and myosin catalytic domain (Agafonov et al., 2010).
Fluorescence Lifetime Plate Reader: This instrument is being developed in collaboration with Fluorescence Innovations, and a prototype has been installed in the BSF. It performs an HPTRF experiment on each well in a 96-well plate reader in seconds, just as fast as a conventional plate reader that reads only fluorescence intensity. This will increase precision and resolution of fluorescence plate-readers by at least an order of magnitude, making it a game-changer in high-throughput drug screening. This instrument has formed the technical foundation of the Minnesota Fluorescence Lifetime Assay Group (MN-FLAG). We will use it for small-molecule screening for heart failure drug discovery.
Competition between PLB mutants: Two important papers (Lockamy et al., 2011; Gustavsson et al., 2011) help establish feasibility for our plan to use site-directed spectroscopy to design new therapeutic PLB mutants for heart failure gene therapy.
DDT was an invited speaker at the Keystone Conferenceon Mechanisms of Cardiac Growth, Death and Regeneration, and he is a finalist for the 2011 NIH Director’s Pioneer Award, for his proposal to lead the above-mentioned biophysical assault on heart failure.
2011: Biophysical Society honors DDTLAB Alum: Congratulations to Diane Lidke, former DDTLAB grad student, for receiving the Margaret O. Dayhoff Award, one of the highest honors bestowed by the Biophysical Society. Diane, Assistant Professor of Pathology at the University of New Mexico, has become a national leader in the use of high-tech fluorescence microscopy to explore the movements and associations of cell-surface receptors involved in cell proliferation, cancer, and the immune response.
2011: Dr. Lennane Michel Espinoza-Fonseca, postdoctoral fellow in the Department of Biochemistry, Molecular Biology and Biophysics, has received Mexico's most prestigious youth award, the 2009 Premio Nacional de Juventud (National Youth Prize) in Academic Achievement. This is the highest academic honor in Mexico for persons under the age of 30. The award consisted of a diploma signed by the President of Mexico, Felipe de Jesús Calderón Hinojosa, a gold medal and 130,000 Mexican pesos (nearly $11,000). The award was granted to Michel in recognition for his scientific work in computational biochemistry and biophysics and for his outstanding academic trajectory, including over 20 peer-reviewed publications. Michel is working with Professor David D. Thomas on the atomic basis of regulation of muscle proteins by using complementary state-of-the-art experiments and computer simulations. Michel's work with Professor Thomas has been published in leading international journals such as the Proceedings of the National Academy of Science, Journal of the American Chemical Society, and the Biophysical Journal. He is supported by a postdoctoral fellowship from the American Heart Association.
2010: DDTLAB Alum, Professor Mike Ostap was named Director of the Pennsylvania Muscle Institute, at the University of Pennsylvania. Mike was Vice Chair, and DDT was Chair of the 2011 Gordon Research Conference on Muscle and Molecular Motors, which will be held July 10-15. Mike will be chair of the 2014 GRC.
2010: Fellowships Awarded: Congratulations to several DDTLAB members for being awarded fellowships: Brett Colson (Postdoctoral Fellowship, NIH), Rebecca Moen (Predoctoral Fellowship, NIH), Michel Espinoza-Fonseca (Postdoctoral Fellowship, American Heart Association), and Simon Gruber (Predoctoral Fellowship, American Heart Association).
2010: Science magazine's November 5th issue mentions DDT's artistic performance from his early years of graduate school in Stanford. Check it out here: http://www.sciencemag.org/cgi/content/full/330/6005/752-b
Transition 2010: Kurt Torgersen graduated from Thomas Lab and landed a scientific position at RKMC LLC in Minneapolis. David Kast, after defending his PhD thesis in May, chose East Coast as his friends Roman and Andrew did and is now thrilled to be in Roberto Dominguez's lab at UPenn.
2009: DDT's collaboration with Celladon Corporation is featured on the UMN's front page and archived here: http://www1.umn.edu/news/news-releases/2009/UR_CONTENT_148812.html
Transition 2009: Andrew Thompson and Roman Agafonov have completed their PhD work and moved as postdocs on the East Coast. Andrew works in Chris Berger's lab at the University of Vermont in Burlington and Roman is currently in Dorothee Kern's lab at Brandeis.
2008: DDT is featured on the Medical School website homepage, in the Snapshots e-magazine, as the Muscle Man.
Transition 2008: Deb Winters, after graduating with a PhD from the lab, works as a scientific advisor at RKMC. Jennifer Klein, PhD, a 2008 graduate also, is currently a postdoctoral fellow on the University's Aging Training Grant.
Transition 2007:
- Jack Surek graduated with a PhD and is now in Boulder CO, as postdoctoral fellow at NIST.
- Two new EPR spectrometers arrived in 2007: a Bruker 580 system, capable of pulsed EPR experiments such as DEER and saturation recovery, and a Bruker 600 W-band system, which features a superconducting magnet that is 10 times stronger than our other two spectrometers.
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EPR spectrometers in Biophysical Spectroscopy Facility: A: Bruker E580 (X-band, 9.4 GHz, pulsed), B: Bruker E600 (W-band, 94 GHz, CW), C: Bruker E500 (X-band, 9.4 GHz, CW). |
Transition 2006: Seth Robia has finished his postdoc stage in Thomas Lab and moved not too far away, at Loyola University in Chicago, IL, as Assistant Professor of Physiology. Two of our Junior Scis, Kari Pedersen and Cory Paterson have been accepted into Pharma and Med Schools, so good luck to them.
Transition 2005: Our collaborator Ed Balogmoved out for a tenured position at Georgia Tech. Cheryl Miller has also left the lab, after 16 years, to prepare business models for an emerging private enterprise.
2005 - DDT was elected chair of the Gordon Muscle Conference, to be held in the summer of 2011, at Colby Sawyer College in New Hampshire. He has also been invited throughout the year to give talks at conferences and symposia such as The 11th International ATPase Conference at Woods Hole, MA in September, The Gordon Conference on Muscle Proteins, in NH in July, and invited talks at major universities in California during his semester leave of last spring.
2004 was very productive for DDT and his collaborators. They published 11 articles in journals such as Proceedings of the National Academy of Sciences, Biophysical Journal, Biochemistry, Journal of Applied Physiology, and Journal of Magnetic Resonance.
DDT was appointed William F. Dietrich Professor in July 2004. The full name of this endowed chair is "William F. Dietrich Land Grant Chair in Fundamental Molecular/Cell Biology in the Basic Sciences." In addition, DDT has been elected Fellow of the Biophysical Society, the highest honor bestowed by the American Biophysical Society. He will receive this award officially at the annual BS Meeting next February in Long Beach.
Transition 2004: During the past year, several lab members have moved on to other positions: congratulations to Josh Baker (former grad student), who has accepted a position as Assistant Professor at the University of Nevada at Reno! Ben Mueller received his PhD and a baby at the same time, and is now completing the clinical part of his MD/PhD training. Tara Kirby moved to the NIDDK at the NIH, where she is a postdoctoral fellow doing X-ray crystallography of membrane proteins. She recently gave birth to a boy, Liam. Wendy Nelson finished her PhD thesis and defended it, and got a postdoc position with Dr. Doris Taylor, who was recently appointed to the Medtronic-Bakken Chair in Cardiac Repair. Former PhD student Diane Lidke and her husband Keith are both doing postdoc work in Goettingen, Germany. Jack Grinband defended his thesis and moved on to postdoctoral work in Neuroscience at Columbia. Vincent Voelz (undergrad) is in grad school at UCSF.
DDT and students were featured in the Winter 2003 issue of Bio. See pages 5(Ben Mueller receives Bloomfield Fellowship.) and 9 (Erika Helgerson and Andrew Jensen help Dr. Thomas pump iron.) BIO, Winter 2003 issue.
Structure of Calcium Pump Regulators: We have used NMR to determine the structure of sarcolipin, a membrane protein that regulates the calcium pump in skeletal muscle. This study, a collaboration between Christine Karim in our lab and Alessandro Mascioni in Gianluigi Veglia's lab (Biochemistry, 41:475-482), involved NMR experiments in detergent solution as well as solid-state NMR on oriented lipid bilayers. This is the first high-resolution structure of a calcium pump regulator in its native lipid environment. The figure at right illustrates hot spots where mutation affects function. [January 02] More recently, we have used similar techniques to determine the structure of phospholamban, which regulates the calcium pump in cardiac muscle (Zamoon et al., Biophys J. 2004). [October 04]
Microwave Magic: Yuri Nesmelov (Postdoctoral Research Associate), in collaboration with Jack Surek (grad student), has created a simple device that increases the sensitivity of EPR for small biological samples by an order of magnitude! Yuri did some calculations on the back of an envelope (a very large one) then designed and fabricated a small hollow cylinder of potassium tantalate that focuses the microwave magnetic field onto the sample placed inside it. The device works for samples placed either parallel or perpendicular to the magnetic field, so it should be a big boost to Jack's thesis work on muscle fiber EPR. Read about it in the Journal of Magnetic Resonance, 153: 7–14. 2001. [October 01]
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How Muscle Works: Using EPR of spin-labeled muscle fibers, we obtained the first direct evidence that the light-chain domain rotates upon muscle activation (PNAS 95: 2944-2949; see figure). Using ATP analogs, Ingrid Brust-Mascher, Leslie Laconte, and Josh Baker showed that the orientations of the light-chain domain in the pre- and post-hydrolysis states are not significantly different from each other (Biochem 38: 12607-12613). This surprising result suggests that the ATP hydrolysis step does not induce a major structural change in myosin; rather the major stuctural change occurs upon strong actin binding and phosphate release. [98-99]
View the powerstroke movies (3.1MB) and the 3D rotation movie (1.49MB)
Cardiac Zipper: Minnesota Musclers Christine Karim and John Stamm and collaborators have obtained a structural model of phospholamban, a protein that helps regulate calcium pumping in the heart. The figure at left shows how leucines (red) and isoleucines (blue) form a "zipper" that holds this protein together in the membrane of a heart cell (Biochem 37: 12074-12081). Laxma Reddy, Ming Li, Bobbi Bennett, and coworkers developed a fluorescence technique for measuring oligomeric state of proteins and showed that the calcium pump binds phospholamban monomers, disrupting the zipper (Biophys J 76: 2587-2599; Biochem 38: 3954-3962). [98-99]