Mitosis: One Polo controls it all

On November 6, 2014, Cell Cycle published a paper from the Yoshida lab entitled “The budding yeast Polo-like kinase Cdc5 is released from the nucleus in anaphase for timely mitotic exit.” This study was authored by Vladimir V. Botchkarev Jr., Valentina Rossio, and Satoshi Yoshida.

The cell cycle is one of the most fundamental biological processes whose ultimate goal is cell division with equal content of DNA in both daughter cells. The process of cell division is regulated by many intracellular events which must occur in a sequential order. These events include mitotic entry, faithful chromosome segregation, mitotic exit, and cytokinesis. Over the past 25 years, the Polo-like kinase (Polo) has been established to play important regulatory roles in each of these processes. Although many mitotic substrates of Polo have been discovered, the mechanism by which Polo can coordinate all of these mitotic events has remained largely elusive.

To understand the mechanism by which Polo can target its many substrates in a sequential order during mitosis, we decided to study the budding yeast Polo kinase Cdc5, which has high conservation with the human Polo-like kinase 1.

We found that Cdc5-GFP dynamically changes its localization during the cell cycle: Cdc5 is found in the cytoplasm in S- through early G2-phase, it accumulates in the nucleus at metaphase, and is released again to the cytoplasm in anaphase. Blocking nuclear import of Cdc5 in metaphase leads to a prolonged metaphase duration, suggesting that nuclear Cdc5 is required for chromosome segregation. In contrast, blocking nuclear release of Cdc5 in anaphase results in a prolonged anaphase duration, a defect in activation of the cytoplasmic Mitotic Exit Network, and a defect in cytokinesis. This indicates that Cdc5 is released from the nucleus to the cytoplasm in anaphase for timely mitotic exit and cytokinesis. We further found that activation of the Cdc14 phosphatase, a known nuclear substrate of Cdc5, is required for Cdc5 nuclear release in anaphase.

Collectively, our work reveals that the budding yeast Polo-like kinase Cdc5 controls the timing of mitotic events by dynamically changing its sub-cellular localization. Furthermore, our data suggests the existence of a positive feedback look between Cdc5 and Cdc14 to regulate timely mitotic exit. Read more

Eve Marder Receives SfN Award

marderEve Marder, PhD, from Brandeis University and Richard Olivo, PhD, from Smith College will receive the Award for Education in Neuroscience from the Society for Neuroscience (SfN). The award will be presented at Neuroscience 2014, SfN’s annual meeting to be held on November 15-19 in Washington, DC.

The $5,000 prize will be split between Drs. Marder and Olivo. It recognizes people who have made outstanding contributions to neuroscience education and training. Dr. Marder played a critical role in the establishment of one of the first undergraduate neuroscience training programs at Brandeis almost 25 years ago. Since then, she has continued to provide advice and support at all academic levels.

Read the SfN press release to learn more about this prestigious award.


Brandeis will host Gene Expression and RNA Seminar (GEARS) meeting this October

Gene Expression and RNA Seminars (GEARS) club is a monthly event that includes scientific talks on the Gene Expression, RNA and Chromatin. Every month it is held at a different institute in the Boston area.

Brandeis University will be hosting the October GEARS meeting on Thursday, October 30 in Rosenstiel 118 from 6:30 – 7.30 PM and will feature three talks from Boston area researchers.  After the talks, there will be a social hour. This event is free and all are welcome to attend.

Speakers List:

“Hijacking an editing enzyme to reveal the targets of RNA-binding proteins”
Aoife McMahon, PhD, Rosbash lab, Brandeis University

“Genome protection against transposons by the piRNA amplifier complex”
Jordi Xiol, PhD, Moazed lab, Harvard Medical School

“Linking cancer metabolism, DNA repair and epigenetics: SIRT6 provides some clues”
Raul Mostoslavsky, PhD, Associate Professor, MGH Cancer Center/Harvard Medical School/Broad Institute

GEARS Club is generously supported with the help of New England Biolabs and Cell Signaling Technology.
This event is also co-sponsored by the Brandeis Biology Office.

For more information please visit:
Twitter @gearsclub

Pioneering geneticist Frederick Alt ’71 wins 44th Rosenstiel Award

Geneticist Frederick Alt ’71 will be awarded the 44th Rosenstiel Award for Distinguished Work in Biomedical Science by Brandeis University for his pioneering research exploring the mechanisms of genomic instability and its implications for the immune system and cancer cells. Alt is the second alumnus to win the Rosenstiel Award; the first, Rod McKinnon ’78, won the Rosenstiel in 1999 and went onto win the Nobel Prize in 2003. Learn more on Brandeis Now …

Odor Recognition & Brute-Force Conversions

Frontiers in Computational Neuroscience will be publishing an interesting paper written by Honi Sanders and John Lisman (with co-authors Brian E. Kolterman, Roman Shusterman, Dmitry Rinberg, Alexei Koulakov) titled, “A network that performs brute-force conversion of a temporal sequence to a spatial pattern: relevance to odor recognition“. Honi Sanders has written a preview of this paper.

by Honi Sanders

Lisman_ProvisionalPDF_BLThere are many occasions in which the brain needs to process information that is provided in a sequence. These sequences may be externally generated or internally generated. For example, in the case of understanding speech, where words that come later may affect the meaning of words that come earlier, the brain must somehow store the sentence it is receiving long enough to process the sentence as a whole. On the other hand, sequences of information also are passed from one brain area to another.  In these cases too the brain must store the sequence it is receiving long enough to process the message as a whole.

One such sequence is generated by the olfactory bulb, which is the second stage of processing of the sense of smell.  While individual cells in the olfactory bulb will fire bursts in response to many odors, the order in which they fire is specific to an individual odor. How such a sequence can be recognized as a specific odor remains unclear.  In Sanders et al, we present experimental evidence that the sequence is discrete and therefore contains a relatively small number of sequential elements; each element is represented in a given cycle of the gamma frequency oscillations that occur during a sniff. This raises the possibility of a “brute force” solution for converting the sequence into a spatial pattern of the sort that could be recognized by standard “attractor” neural networks.  We present computer simulations of model networks that have modules; each model can produce a persistent snapshot of what occurs during a given gamma cycle. In this way, the unique properties of the sequence can be determined at the end of sniff by the spatial pattern of cell firing in all modules.

The authors thank Brandeis University High Performance Computing Cluster for cluster time. This work was supported by the NSF Collaborative Research in Computational Neuroscience, NSF IGERT, and the Howard Hughes Medical Institute.

Genetics Training Grant Retreat to be held Friday, 9/26/14

The annual Genetics Training Grant seminar is being held on Friday, September 26th at the Shapiro Campus Center Auditorium at Brandeis University. Four cutting-edge synthetic biologists: Timothy Lu, Ron Weiss, William Shih and Ahmad Khalil will share their research for the Synthetic Biology: Insights and Applications” symposium.
Brandeis graduate students and post-docs will have the opportunity to meet the speakers and present their work in a poster session after the talks. We encourage researchers from all departments to contribute. If you are currently, or previously were on the Genetics Training Grant, presentation of a poster is expected. 

Schedule for GTG Retreat

9:30-10:30 Ron Weiss (MIT, Dept. of Biological Engineering)
“Synthetic biology: from parts to modules to therapeutic systems.”
10:30-11:00 Coffee Break
11:00-12:00 Timothy Lu (MIT, Dept. of Biology Engineering)
“Synthetic biology for human health applications.”
12:00-1:30 Break/Lunch
1:30-2:30 William Shih (Wyss Institute)
“DNA nanostructures as building blocks for molecular biophysics and future therapeutics.”
2:30-3:30 Ahmad Khalil (Boston University, Biomedical Engineering)
“Building molecular assemblies to control the flow of biological information.”
3:30-5:00 Poster session
Shapiro Science Center 2nd floor.
All life sciences students are invited to present.

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