Related Readings: Brian K. Kobilka, M.D.

Friday Lecture Series

Structure and Dynamics of the Human β 2 Adrenergic Receptor

Brian K. Kobilka, M.D.

Professor of Medicine and Molecular and Cellular Physiology

Stanford University School of Medicine

3:15 pm – Refreshments, Abby Lounge

3:45 pm – 5:00 pm – Lecture, Caspary Auditorium

The Rockefeller University Campus

Recommended Articles:

Deupi, X., and Kobilka, B.  2007.  Activation of G Protein-Coupled ReceptorsAdvances in Protein Chemistry 74 :137-166.

Kobilka, B., and G.F.X. Schertler.  2008.  New G-protein-coupled receptor crystal structures: insights and limitations.  Trends in Pharmacological Sciences 29 (2):79-83.

Cherezov, V., et al.  2007.  High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptorScience 318 (5854):1258-1265.

Rasmussen, S.G.F., et al.  2007.  Crystal structure of the human β2 adrenergic G-protein-coupled receptorNature 450 (7168):383-387.

Kobilka, B.K., and Deupi, X.  2007.  Conformational complexity of G-protein-coupled receptorsTrends in Pharmacological Sciences 28 (8):397-406.

Kobilka, B.K.  2007.  G protein coupled receptor structure and activationBiochimica et Biophysica Acta – Biomembranes 1768 (4):794-807.

 

Related Readings: Hugh Cam, Ph.D.

Monday Lecture Series

Epigenetic Control and Genome Organization by RNAi and Transposon-derived Proteins

Hugh Cam, Ph.D.

Postdoctoral Fellow, Laboratory of Biochemistry and Molecular Biology

National Cancer Institute, National Institutes of Health

3:45 pm – Refreshments,  4:00 pm – Lecture

Welch Hall, 2nd Floor

Rockefeller University Campus

 

Recommended Articles:

Cam H.P., Sugiyama T., Chen E.S., Chen X., FitzGerald P.C., Grewal S.I.S.  2005.  Comprehensive analysis of heterochromatin- and RNAi-mediated epigenetic control of the fission yeast genome.  Nature Genetics. 37 (8):809-819.

Dutrow, N., Nix, D.A., Holt, D., Milash, B., Dalley, B., Westbroek, E., Parnell, T.J., Cairns, B.R.  2008.  Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mappingNature Genetics. 40 (8):977-986.

Chapman, E.J., Carrington, J.C.  2007.  Specialization and evolution of endogenous small RNA pathways.  Nature Reviews Genetics. 8 (11):884-896. 

Bühler, M., Haas, W., Gygi, S.P., Moazed, D.  2007.   RNAi-Dependent and -Independent RNA Turnover Mechanisms Contribute to Heterochromatic Gene SilencingCell. 129 (4):707-721.
Articles that cite this paper.

Peng, J.C., Karpen, G.H.  2008.  Epigenetic regulation of heterochromatic DNA stability.  Current Opinion in Genetics and Development. 18 (2):204-211.

Hansen, K.R., Burns, G., Mata, J., Volpe, T.A., Martienssen, R.A., Bähler, J., Thon, G.  2005.  Global Effects on Gene Expression in Fission Yeast by Silencing and RNA Interference Machineries.  Molecular and Cellular Biology. 25 (2):590-601.

Roles of Microorganisms in Diseases Uncovered

In a variety of today’s headlines in the world of science and medicine, the ubiquitous bacteria warrant special mention.  In our last blog posting, we described the alarming concern over antibiotic resistance.  Today, current information provides us with on an overarching view of some ethics and social implications of the Human MicrobiomeProject, and then we drill down into the details of some recent microbiological discoveries that have been reported in the scientific literature.
On Friday, September 19, a regarded online publication named GenomeWeb Daily News reported that the National Institutes of Health plan to address the ethical, legaland social implications of the Human Microbiome Project (HMP).  A brief definition of the project can be found here.  In essence, HMP is proposed as a feasibility study with “the goal of identifying and characterizing the microorganisms which are found in association with both healthy and diseased humans” (from Wikipedia.org).
Social and ethical questions surround HMP which include questions about potential clinical applications of this research, the implications for health and for society, and privacy concerns for groups, individuals and families associated with the research.  It’s important that these aspects are studied by the NIH and three awards of hundreds of thousands of dollars are available over the three-year timetable for this project.

Enter the lowly bacterium…
 
Several scientific headlines have been snatched by bacteria during the past couple of days.  The first article of note also gives credit to the eukaryotic Candida albicans, where researchers from Beth Israel Deaconess Medical Center, Boston, and Harvard Medical School, Boston describe prokaryotic-eukaryotic interactions of Acinetobacter baumannii and C. albicans as identified using the common nematode Caenorhabditis elegans.  A paucity of data exists on the bacterial-fungal encounters within a living host and in this study, A. baumannii inhibited virulence of C. albicans.  This in vivo work supports existing in vitro studies.  The study provides a whole-animal model to open the door to investigating the dynamics of polymicrobial infections.
Another study reported in the October issue of the Journal of Medical Microbiology received recognition  today when several articles described the interactions of the gut bacterium Enterococcus faecalis and colon cells (Medical News Today, September 22, 2008, “Gut Bacterium Linked to Colon Cancer”, www.medicalnewstoday.com, ScienceDaily, September 22, 2008, “Cancer-causing Gut Bacteria Exposed”, www.sciencedaily.com/releases/2008/09/08092120171.htm, Allen, T.D., et al., 2008.  Dichotomous metabolsim of Enterococcus faecalis induced by haematin starvation modulates colonic gene expression.  J Med Microbiol 57:1193-1204.)  This bacterium can survive using respiration or fermantation, and when it relies on the latter metabolic processes it releases superoxide, which leads to signalling in macrophages.  Superoxide also increades the productivity of genes that are associated with cancer.
In another host/bacterium study, investigators at the University of Chicago and Yale University demonstrated that when mice were exposed to some forms of bacteria the onset of Type I diabetes may be prevented by upsetting this autoimmune disease.  In a paper published in Nature, Li Wen at Yale and Alexander V. Chervonsky at the University of Chicago demonstrated that non-obese diabetic (NOD) mice were significantly less likely to develop diabetes when exposed to harmless gut bacteria.  Understanding the balance of the bacterial / disease interaction is important for understanding the underlying basis for the disease.
Initiatives to better understand the Human Microbiome and studies that publish data to help understand disease / bacterial interactions move us closer to understanding our links with the microbiological world.  The use of probiotics has been suggested in the popular press for establishing healthy microflora.  Now, we may be more dependent upon our microflora for good health than we ever thought imagineable in the past.

British Medical Journal Editorial Outlines Need to Tackle Antibiotic Resistance

Professor Otto Cars from Infectious Diseases, Department of Medical Sciences, Uppsala University, Uppsala, Sweden, et al. present disturbing evidence that a well-coordinated global response is needed to prevent a pandemic of antibiotic resistance BMJ 2008;337:a1438In the September 18, 2008 publication, Cars unravels a story that began almost eight decades ago when the first antibiotics were used to treat infections.  The use and misuse of antibiotics threatens to take the world back to a pre-antibiotic era with sobering consequences that would impede surgery, organ transplantation, cancer chemotherapy, and a myriad of other healthcare advances.

Low income and middle income countries have poor treatment rates (e.g. 70% of nosocomial neonatal infections could not be successfully treated by using WHO’s recommended regimen).  In high income countries, the number of methicillin resistant Staphylococcus aureus related deaths has increased 30-fold between 1993 and 2006.  To overcome these statistics, the authors call for leadership on international and national levels, changes in consumer and provider behaviors, and better development of effective antibacterial agents to match current need.

The editorial also describes how fundamental problems in sanitation and the lack of safe water contribute to the overuse of antibiotics as a quick-fix solution to avoid disease.  And as existing antibiotics decline in their effectiveness, the discovery of new antibiotics is also declining.  Innovation and the discovery of new antibacterial agents has been meager in recent years; less than 2% of all drugs in development at the world’s largest pharmaceutical companies are antibiotics and there still remains unmet needs for treating some Gram negative infections.

Summary points listed in the article include:

  • “Antibiotics are a prerequisite for many of the advanced technologies in today’s healthcare”
  • “Although antibacterial resistance is growing, development of new antibiotics has declined”
  • “A new paradigm in which antibiotics are considered as a non-renewable resource is needed”
  • “The know-do gap in control of bacterial resistance to antibioticsmust be tackled on international, national, and individual levels”

Obama and McCain Answer Top 14 Science Questions

Who is the best choice for president in an increasingly science dominated society?  38,000 scientists and their professional organizations developed a ‘short list’ of questions to provide insight for everyone on the science savvy of the two top presidential candidates.  These fourteen questions represent the most compelling science issues we face in the near future.  Read the candidates’ responses side-by-side on the “Science Debate 2008” website.

Related Readings: Tadashi Nakaya

Seminar 

A novel intracellular signaling pathway mediated FE65 and APP

 

Tadashi Nakaya, Ph.D.

Head of Laboratory, Hokkaido University

Graduate School of Pharmaceutical Sciences

 

10:00 am – 11:00 am, Monday, September 15, 2008

15th Floor Conference room, WRB

 

Recommended Review Article:

McLoughlin, D.M.; & Miller, C.C.J.  2008.  The FE65 proteins and Alzheimer’s disease.  Journal of Neuroscience Research.  86(4):744-754.  (please order copies from the Markus Library)

Related Articles:

Nakaya, T.; Kawai, T.; & Suzuki, T.  2008.  Regulation of FE65 Nuclear Translocation and Function by Amyloid β-Protein Precursor in Osmotically Stressed CellsThe Journal of Biological Chemistry.  283(27):19119-19131.

Müller, T.; et al.  2008.  The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics—Relevance for Alzheimer’s diseaseProgress in Neurology.  85(4):393-406.

Nakaya, T.; & Suzuki, T.  2006.  Role of APP phosphorylation in FE65-dependent gene transactivation mediated by AICDGenes to Cells.  11(6):633-645.

 

Schistosomes: Vector for Gene Therapy?

Gene delivery helped by deadly worm

10-Sep-2008 –

Gene therapy could be advanced by a worm more commonly associated with causing a deadly parasitic disease, according to researchers presenting at the British Pharmaceutical Conference (BPC).

The researchers believe that a protein secreted by the eggs of Schistosoma mansoni could act as a vector to insert genes into the target genetic material.

Read more…..

Cryptococcus Cells Invade by Stealth via Vomocytosis

Cryptococcus, a lethal complication for many HIV AIDS victims, like HIV itself, bends the body’s defenses to its own diabolical purposes.  The fungus cells hide in macrophages, tour the body, and invade and replicate without destroying the host macrophage and triggering an immune reponse.   Read more about this research presented at the 2008 meeting of the Society for General Microbiology by researchers from the University of Birmingham.

NIH Grants to Lower Hurdles for Transformative Research

NIH Details $250M Program for Supporting ‘Transformative’ Research

By a GenomeWeb staff reporter   Sept 10, 2008

 

NEW YORK (GenomeWeb News) – The National Institutes of Health today issued details of a $250 million plan to fund “transformative” research through a new type of grants that are designed to lower the hurdles researchers face as they try to win backing for “bold [and] creative” science.

Read More…