Seminars

2013/06/07 12:00

ATRIO 800

Jesús Rodríguez Requena, PhD (CIMUS Biomedical Research Institute, University of Santiago de Compostela, Spain)

The structure of PrPSc in search of the 'double helix' of prions

Prions are infectious proteins that transmit deadly neurodegenerative diseases. More broadly, prions are proteins that store and transmit information, a property previously thought to be exclusive of nucleic acids. Prion-like information transmission might be more common than thought, and might play a role in key biological processes such as self/non-self recognition, memory, and amyloid diseases in general. But how do prions work? They store information conformationally: all known prions are amyloids, and it is conceivable that their "information code" consists of non-covalent bonds between amino acids not unlike base-pairing in nucleic acids. Just as the mechanism of nucleic acid-based transmission of information was immediately obvious once the structure of DNA was solved, solving the structure of prions will lead to an understanding of how they work. However, deciphering the structure of prions is not an easy task, given their aggregated, insoluble nature. Some tantalizing data based on cryo-electron tomography and microscopy, and biochemical approaches will be presented. Structural data from several groups, including ours, is beginning to reveal the code of protein-based information transmission.

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2013/06/14 12:00

Atrio 800

Marc Claret, PhD (Institut d’Investigacions Biomèdiques August Pi iSunyer (IDIBAPS), Barcelona, Spain.)

Mitochondrial fusion proteins in hypothalamic POMC neurons regulate whole-body energy homeostasis

In recent years, the mediobasal hypothalamus has been firmly established as a key area of the central nervous system implicated in the regulation of whole-body energy homeostasis. This is achieved through a complex sensing of hormones and nutrient-related signals, followed by its integration and coordination of precise neurochemical and neurophysiological responses. These effector mechanisms are critically mediated by specific populations of neurons of the arcuate nucleus of the hypothalamus. In particular, neurons expressing anorexigenic pro-opiomelanocortin (POMC) precursor have been extensively implicated in the regulation of appetite, body weight and metabolism. The precise molecular mechanisms by which POMC neurons are able to sense energy/nutritional cues are incompletely understood, although a number of sensing molecules (AMPK, SIRT1, mTOR) have been reported to play relevant roles in energy balance control. Interestingly, the activity of these proteins may be modulated by metabolic mitochondrial intermediates, and therefore the mitochondria can be viewed as an energy-sensing organelle. Mitochondrial dynamics is a process regulated by nutrient availability, so fusion and fission events may represent primary nutrient/energy sensing processes implicated in the hypothalamic regulation of energy balance. Using a combination of conditional mouse genetics, detailed physiology, electron microscopy and molecular biology our current studies reveal a novel role for mitochondrial fusion proteins in the hypothalamus in the control of body weight and glucose metabolism.

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2013/06/28 12:00

ATRIO 800

Kornelius Zeth, PhD (Unidad de Biofísica-UPV)

Killing bacteria - the power of natural antibiotics

Uni- and multicellular organisms have developed smart methods to combat and kill bacteria. Many bacteria secret bacteriocins or proteins of the Cdi system to target and kill related or unrelated bacterial strains of the same culture, respectively. These narrow or broad band antibiotics typically comprise entire proteins, which unselectively destroy cellular components such as DNA, RNA, Peptidoglycane of they can permeabilize the inner membrane to disrupt the inner membrane potential. In mammalian, protection against bacterial or funghal treatment is induced by the production of antimicrobial peptides (AMPs). This battery of defense peptides can compromise the integrity of microbial cell membranes and thereby evade pathways by which bacteria develop rapid antibiotic resistance through mutations. Although more than 2000 host defense peptides from diverse origin have been described, the structural and mechanistic basis of their activity remains largely unknown. In order to understand the mechanism by which AMPs can compromise cell membranes we performed structure biology, electrophysiology, and MD simulations on one example, the human dermcidin (DCD) in membranes. This talk aims to give a glimpse on the targeting mechanisms of natural antibiotics. and points of bacterial membranes as a unique target for antibiotic attack.

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2013/07/19 12:00

Atrio

Special Lecture Prof. Lewis Kay (Department of Biochemistry - University of Toronto)

2013/09/27 12:00

ATRIO 800

Ricardo Flores, PhD (Universidad Politécnica de Valencia)

Viroids: the simplest (and most ancient?) RNA replicons

Despite their name, viroids are structurally, functionally and evolutionarily independent of viruses. Viroids are exclusively composed by a small circular RNA of 250-400 nucleotides (one order of magnitude lower than the smallest viral genomes), without protein-coding ability (all viruses encode in their genomes one or more proteins). Besides, some viroid RNAs display catalytic activity, in other words, contain ribozymes (of the hammerhead class) that mediate their replication. This last property, together with their structural simplicity, has led to regard viroids as molecular fossils of the «RNA World» presumed to have preceded our present-day world base on DNA and proteins. Therefore, viroids seem to fulfill the paradigm that the simplest is the oldest. In addition to their academic interest, viroids incite diseases in plants economically relevant and, consequently, they also have an applied side. Pathogens of this class have not been described so far in animals, although the RNA of human hepatitis delta virus shares remarkable parallelisms with viroids.

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2013/10/04 12:00

Atrio 800

Prof. Charles Coombes (Imperial College London)