Drake C. Mitchell, PhD, Section Chief
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
5625 Fishers Lane, Room 3N07:MSC 9410
Bethesda MD 20892-9410
telephone: +1 301 496 4452
fax: +1 301 594 0035
e-mail: dmitch@mail.nih.gov
Mission Statement
- Applies the techniques of fluorescence polarization, anisotropy and lifetimes as well as other spectrophotometric and biophysical approaches to the problem of specialization in membrane structure with respect to polyunsaturated phospholipids;
- defines microdomains as well as selective lipid-protein and lipid-lipid interactions within plasma membranes in order to allow a more detailed investigation into the perturbations in membrane structure caused by acute or chronic alcohol treatment. The localization of hexaenoic species of aminophospholipid will be of particular interest in this regard;
- explore the utility of a variety of novel fluorescent phospholipid probes prepared by partial synthesis for these studies;
- investigate more general features of the biophysical effects of ethanol on membrane structure and organization; and
- collaborate closely with others in the laboratory working on related problems and, particularly, with the NMR Section.
Current staff
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Shui-Lin Niu, PhD
Staff Scientist
301.435.6728
sniu@mail.nih.gov
Current projects: Delineating the mechanisms whereby membrane composition and membrane lateral architecture alter the functionality of G proteins and their effectors, with an emphasis on high-speed, dynamic techniques. Determining the relative binding affinities of fatty acid binding proteins for omega-3 and omega-6 polyunsaturated fatty acids using isothermal titration calorimetry. |
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Kirk Hines, MS
Biologist
301.443.1101
khines@mail.nih.gov
Current projects: Purifying and characterizing a number of unique, highly polyunsaturated phospholipids from retinal rod outer segment disk membranes. Using differential scanning calorimetry to establish the heterogeneity of phospholipid and sterol components of biological membranes
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Jessica Kloda, PhD
Postdoctoral IRTA
301.443.8317
hodenj@mail.nih.gov
Current projects: Determining the effects of omega-3 deficient diet on GABAA receptor function using electrophysiological techniques and microtransplantation of purified synaptic plasma membranes into Xenopus oocytes. Examining the effects of omega-3 and omega-6 polyunsaturated fatty acids on the function and pharmacology of various isoforms of the GABAA receptor as well as the glycine receptor.
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Michael Bennett, PhD
Postdoctoral IRTA
301.443.1101
bennettmp@mail.nih.gov
Current projects: Assessing the role of omega-3 and omega-6 polyunsaturated phospholipids in determining the thermal stability of integral membrane proteins using differential scanning calorimetry. Examining the interplay between membrane polyunsaturated phospholipid content, membrane microdomains and membrane acyl chain packing using a variety of time-resolved fluorescence techniques.
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Dawn Barnes, BS
Postbac IRTA
301.435.8317
barnesdawn@mail.nih.gov
Current projects: Assessing the effects of omega-3 deficient diet on the ability of the GABAA receptor to bind sedatives and other drugs, using synaptosomes purified from rats raised on omega-3 adequate and deficient diets and radioligand binding.
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Brian Anderson, BS
Postbac IRTA
301.435.6729
hodenj@mail.nih.gov
Current projects: Developing a preparative procedure for preparing phospholipid vesicles that ensures that reconstituted receptors are uniformly vectorially inserted in the membrane. Analyzing membrane acyl chain packing and water permeability in membrane-containing membranes using time-resolved fluorescence.
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Collaborator
Dr. Albert Jin and Dr. Paul Smith; Instrumentation Research and Development Branch, Division of Bioengineering and Physical Science, Office of Research Services.
Dr. Fuyuki Tokumasu & Dr. James Dvorak; Biochemical and Biophysical Parasitology Section, Laboratory of Malaria and Vector Research, NIAID
Dr. Barbara Wiggert; Biochemistry Section, Laboratory of Retinal Cell and Molecular Biology, NEI
Dr. Eric Murphy, Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine
Dr. Lee Richter, Surface Dynamical Processes Group and Dr. Kimberly Briggman, Laser Applications Group; National Institute of Standards and Technology
Dr. Martha Neuringer, Department of Neuroscience, Oregon Health Sciences University
Selected Recent Publications
SL Niu, DC Mitchell, BJ Litman: Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced activation as compared to their cis analogs. Biochemistry. 44(11):4458-4465, 2005. PubMed
Niu SL, Mitchell DC. Effect of packing density on rhodopsin stability and function in polyunsaturated membranes. Biophys J. 89(3):1833-1840, 2005. PubMed [PDF]
Ellis CE, Murphy EJ, Mitchell DC, Golovko MY, Scaglia F, Barcelo-Coblijn GC, Nussbaum RL. Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein. Mol Cell Biol. 25(22):10190-10201, 2005. PubMed [PDF]
Niu SL, Mitchell DC, Lim SY, Wen ZW, Kim HY, Salem N Jr., Litman BJ. Reduced G Protein-coupled Signaling Efficiency in Retinal Rod Outer Segments in Response to n-3 Fatty Acid Deficiency. J Biol Chem. 279(30):31098-31104, 2004. PubMed [PDF]
E. Choi, AJ Jin, SL Niu, PD Smith, and BJ Litman. Visualizing Individual Rhodopsin (a G Protein-Coupled Receptor) Molecules in Native Disk and Reconstituted Membranes via Atomic Force Microscopy Nanontech 2004 Proceedings (2004).
DC Mitchell, SL Niu, and BJ Litman, Enhancement of G protein coupled signaling by DHA phospholipids, Lipids 38:437-443 (2003). PubMed
Mitchell DC, Niu SL, Litman BJ. DHA-rich phospholipids optimize G protein-coupled signaling. J Pediatrics. 143(4 Suppl):S80-S86 (2003). PubMed [PDF]
Mitchell DC, Niu SL, Litman BJ. Enhancement of G protein coupled signaling by DHA phospholipids. Lipids 38(4):437-443, 2003. PubMed [PDF]
Jeffrey BG, Mitchell DC, Gibson RA, Neuringer M. n-3 fatty acid deficiency alters recovery of the rod photoresponse in rhesus monkeys. Inv Opth Vis Sci. 43:2806-14. 2002. PubMed
Jeffrey BG, Mitchell DC, Hibbeln JR, Gibson RA, Chedester AL, Salem N Jr. Visual acuity and retinal function in infant monkeys fed long-chain PUFA. Lipids. 37(9):839:848, 2002. PubMed [PDF]
Koenig BW, Kontaxis G, Mitchell DC, Louis JM, Litman BJ, Bax A. Structure and orientation of a G protein fragment in the receptor bound state from residual dipolar couplings. J Mol Biol. 322(2):441-461, 2002. PubMed
Niu SL, Mitchell DC, Litman BJ. Manipulation of cholesterol in rod disk membranes by methyl-β-cyclodextrin: effects on receptor activation. J. Biol. Chem. 277(23):20139-201345, 2002. PubMed
Weisinger HS, Armitage JA, Jeffrey BG, Mitchell DC, Moriguchi T, Sinclair AJ, Weisinger RS, Salem N Jr. Retinal sensitivity loss in third-generation n-3 PUFA-deficient rats. Lipids. 37(8):759-765, 2002. PubMed [PDF]
Jeffrey BG, Mitchell DC, Hibbeln JR, Gibson RA, Chedester AL, Salem N Jr. Visual acuity and retinal function in infant monkeys fed long-chain PUFA. Lipids. 37(9):839-848, 2002. PubMed [PDF]
Niu SL, Litman BJ. Determination of membrane cholesterol partition coefficient using a lipid vesicle–cyclodextrin binary system: effect of phospholipid acyl chain unsaturation and headgroup composition. Biophys J. 83(6):3408-3415, 2002. PubMed
Litman BJ, Niu SL, Polozova A, Mitchell DC. The Role Of Docosahexaenoic Acid Containing Phospholipids In Modulating G Protein-Coupled Signaling Pathways: Visual Transduction. J Mol Neurosci. 16(2-3):237-242, 2001. PubMed [PDF]
Jeffrey BG, Weisinger HS, Neuringer M, Mitchell DC. The Role of Docosahexaenoic Acid in Retinal Function. Lipids. 36(9):859-871, 2001. PubMed [PDF]
Mitchell DC, Niu SL, Litman BJ. Optimization of receptor-G protein coupling I: kinetics of rhodopsin-transducin binding. J Bio. Chem. 276(46):42801-42806, 2001. PubMed
Niu SL, Mitchell DC, Litman BJ. Optimization of receptor-G protein coupling II: formation of the metarhodopsin II-transducin complex. J Biol Chem. 276(46):42807-42811, 2001. PubMed
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