Psr1p interacts with SUN/sad1p and EB1/mal3p to establish the bipolar spindle

Regular Abstracts - Sunday Poster Presentations: no. 382During mitosis, interpolar microtubules from two spindle pole bodies (SPBs) interdigitate to create an antiparallel microtubule array for accommodating numerous regulatory proteins. Among these proteins, the kinesin-5 cut7p/Eg5 is the key player responsible for sliding apart antiparallel microtubules and thus helps in establishing the bipolar spindle. At the onset of mitosis, two SPBs are adjacent to one another with most microtubules running nearly parallel toward the nuclear envelope, creating an unfavorable microtubule configuration for the kinesin-5 kinesins. Therefore, how the cell organizes the antiparallel microtubule array in the first place at mitotic onset remains enigmatic. Here, we show that a novel protein psrp1p localizes to the SPB and plays a key role in organizing the antiparallel microtubule array. The absence of psr1+ leads to a transient monopolar spindle and massive chromosome loss. Further functional characterization demonstrates that psr1p is recruited to the SPB through interaction with the conserved SUN protein sad1p and that psr1p physically interacts with the conserved microtubule plus tip protein mal3p/EB1. These results suggest a model that psr1p serves as a linking protein between sad1p/SUN and mal3p/EB1 to allow microtubule plus ends to be coupled to the SPBs for organization of an antiparallel microtubule array. Thus, we conclude that psr1p is involved in organizing the antiparallel microtubule array in the first place at mitosis onset by interaction with SUN/sad1p and EB1/mal3p, thereby establishing the bipolar spindle.postprin

Mammalian comparative genomics and epigenomics

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references.The human genome sequence can be thought of as an instruction manual for our species, written and rewritten over more than a billion of years of evolution. Taking a complete inventory of our genome, dissecting its genes and their functional components, and elucidating how these genes are selectively used to establish and maintain cell types with markedly different behaviors, are key challenges of modern biology. In this thesis we present contributions to our understanding of the structure, function and evolution of the human genome. We rely on two complementary approaches. First, we study signatures of evolutionary processes that have acted on the genome using comparative sequence analysis. We generate high quality draft genome sequences of the chimpanzee, the dog and the opossum. These species share a last common ancestor with humans approximately 6 million, 80 million and 140 million years ago, respectively, and therefore provide distinct perspectives on our evolutionary history. We apply computational methods to explore the functional organization of the genome and to identify genes that contribute to shared and species-specific traits. Second, we study how the genome is bound by proteins and packaged into chromatin in distinct cell types. We develop new methods to map protein-DNA interactions and DNA methylation using single-molecule based sequencing technology. We apply these methods to identify new functional sequence elements based on characteristic chromatin signatures, and to explore the relationship between DNA sequence, chromatin and cellular state.by Tarjei Sigurd Mikkelsen.Ph.D

Children's cognition of tonal organisation as measured by reaction time.

This study examined perceptual and cognitive structures that children employ\ud when listening to musical pitches. A number of experiments utilised reaction\ud time as the dependent variable to identify perceptually salient factors in musical\ud pitch perception, particularly the cognitive organisation of musical pitch in a\ud tonal context. A chronometrically measured forced-choice paired—comparisons\ud experimental paradigm was used with children between the ages of six and\ud eleven, with the discrimination of same and different notes in context-free and\ud various contextual presentations tested by a computer—driven environment.\ud Significant correlations suggest that the recognition of same and different notes\ud in both context-free and contextual presentations was progressively facilitated,\ud with responses exhibiting fewer errors and decreasing reaction times with\ud increasing age.\ud Although no significant difference was observed in mean correct reaction times\ud between uncontextualised same and different conditions, significant\ud differences in reaction times were observed within each condition when suffix\ud notes were each contextualised by a major triad prefix. Furthermore, while no\ud significant correlation was observed between same and different notes in\ud context-free presentation, the subsequent contextualisation by a major triad\ud prefix to each comparison suffix note produced a significant positive correlation\ud suggesting that the contextualisation effects were systematic.\ud A further experiment using a diminished triad prefix confirmed that the tonal\ud specificity of the stimuli was related to the observed reaction times, with\ud significant differences in correct reaction times for those stimuli which differed\ud in the tonal range of their constituent pitches in relation to the circle of fifths.\ud The observed differences in the reaction time of responses were interpreted as\ud differential measures of the internalisation of musical pitches to a cognitive\ud structure such as a tonal schema. The hypothesis that perceptual facilitation of\ud the coding of redundancy within such a recognised and practised cognitive\ud structure such as tonality was supported for children of this age