PRBB-CRG Sessions Paul Nurse The Francis Crick Institute, London UK "Controlling the Cell Cycle"
Host: Luis Serrano (CRG)
Abstract: Both S-phase and mitosis are common to all cell cycles and both are necessary for the two newly divided cells to receive a full complement of genes. In fission yeast the onset of S-phase and mitosis can be controlled by a single cyclin dependent kinase with different levels of CDK activity bringing about progression through the cell cycle in an orderly fashion. A low CDK activity is sufficient to bring about S-phase whilst a high activity blocks a further S-phase and is needed for onset of mitosis. A G2 cell can be programmed to undergo either S-phase or mitosis simply by modifying CDK activity indicating there is no inherent direction in the cell cycle.
PRBB-CRG Sessions Sergei Nedospasov Molecular Immunology, Engelhardt Institute of Molecular Biology, and A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State University, RU "to be determined"
PRBB-CRG Sessions Edwin Cuppen Hubrecht Institute and Deparment of Medical Genetics, University Medical Center Utrecht, Utrecht NL "Decoding structural variation in genomes"
Host: Anna Houben (CRG)
Abstract: Advances in DNA sequencing now make it possible to determine complete genome sequences of individuals. However, our understanding of the genetic basis of disease is still limited due to an incomplete knowledge of functional genomics elements and the impact of various types of genetic variations on them. In practice, cost limitations, but also due to our limited knowledge on the function and effects of genetic variation in non-coding genomic region, most studies for the identification of causal pathogenic variation in patients focus on the analysis of exomes. However, these approaches typically ignore the effects of structural variation, including copy number variations, but also copy-neutral events like inversions and translocations. From a large body of literature, it is clear that such variation is an important contributor to congenital syndromes but also cancer. Such variation is not readily detected by routine NGS analysis. We have applied long mate-pair sequence analysis to family trio’s including patients with severe congenital abnormalities as well as to a range of cancer samples. We show that this method is highly sensitive for detecting all types of structural variants. Furthermore, we discovered that a process called chromothripsis that was recently described for somatic cancer cells to cause complex genomic rearrangements, also contributes to complex de novo germline variation and disease. While these complex structural events are likely to be the cause of the disorder, understanding the underlying disturbed biology does not necessarily emerge from the rearranged genomic structure. I will present our systematic molecular characterization approach that uses RNA-seq, ChIP-seq and 4C methods to dissect the effects of rearranged chromosomal fragments and to identify the pathogenic driver event(s).
PRBB-CRG Sessions Marco Capogna Anatomical Neuropharmacology Unit, Medical Research Council, Oxford UK "Theta network oscillations: focus on GABAergic cells of amygdala and hippocampus"
Host: Mara Dierssen (CRG)
Abstract: Dr. Capogna's talk will focus on the contribution of specific GABAergic cell types of the amygdala and hippocampus to neural network oscillations. Brain rhythms occur during arousal, locomotion, mnemonic process, and sleep, and can be partially disrupted in psychiatric diseases. The speaker will show that different types of GABAergic neurons are active at different phases of hippocampal neuronal oscillations thereby controlling the activity of postsynaptic cells at different times. Dr. Capogna will illustrate that GABA-A receptor-mediated events elicited by various interneuron types display distinct duration and synaptic plasticity, and that these factors are crucial in determining their physiological influence on target neurons. The mechanisms underlying the time course and the dynamic properties of inhibitory synaptic responses will be discussed.
PRBB-CRG Sessions Gia Voeltz Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder (CO) US "New roles for ER structure and dynamics at organelle contact sites"
Host: Pedro Carvalho (CRG)
Abstract: The ER has an elaborate and dynamic structure that is conserved throughout eukaryotes. We are interested in how ER shape is regulated to generate a functional organelle. We have studied three major mechanisms that influence the 3-D structure of the ER. ER shape is determined by membrane shaping proteins, dynamics on the cytoskeleton, and interactions with other organelles. These forces work together to distribute this organelle throughout the cytoplasm and generate the complexity of ER functional domains. In turn, we have recently demonstrated that ER shape and dynamics also influence the distribution and dynamics of other organelles. I will discuss the dynamic interplay between the various mechanisms that regulate the elaborate structure of the ER and the organelles that it contacts.
PRBB-CRG Sessions Stephen Blacklow Dept.of Cancer Biology, Dana-Farber Cancer Institute & Dept.of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston (MA) US "to be determined"