And the big paper is in press

Our manuscript is accepted in the Biochemical Journal.  It is a too brief moment of satisfaction of completing a project.  A special thanks to the experimentalists who succeeded in converting the complex problem of cell division with damaged DNA into a powerful experimental model. Of the cell lines we tested, HT-29 cells have features that provide a window of the key transition point of entry into mitosis after a checkpoint. 
What's next - we have developed a non-radioisotope assay to measure enzyme activity in mitotic cells; we are testing how to block checkpoint adaptation, and we are looking very closely at the DNA in cancer cells that survive checkpoint adaptation. 
If interested, please feel free to contact us for questions, reagents or a copy of the paper.

Canada Wide Science Fair in Lethbridge 2013

The Southern Alberta Technology Council and the University of Lethbridge are hosting the Canada Wide Science Fair 2013.  During 11-18 May 2013, 400 of Canada's finest school aged children will present their science projects to expert judges. Based upon previous national, regional and local sciences fairs, we are expecting another eye-opening and impressive week of science.  The students have tremendous energy and imagination that they channel into projects about astronomy, chemistry, information technology and biology.  I am the local Chief Judge responsible for organizing a 400 member judging team that must meet the standard set by Canada's best students.  The stakes are high.  We must nuture a young scientific spirit while choosing the best projects that will share $1,000,000 in prizes and scholarships.

If you would like to be a judge and you have a science or technology background and live within driving distance (AB, BC, Sask), please contact me. 

roy.golsteyn@youthscience.ca

If you want to support everyone's future, support Youth Science Canada:

http://youthscience.ca/

And in any case, mark your calendars so that you can meet Canada's best in Lethbridge. 

Winners 2012 Charlottetown
http://youthscience.ca/

Mitotic catastrophe and genomic rearrangement

A very interesting publication by Stephens and colleagues highlights how human cells can survive after massive genomic rearrangement.  By the technique of whole genome sequencing, they identify chromosomes that have been broken and then reassembled.  Strikingly, the chromosomes are not always reassembled into the original sequence.  It might be compared to shattering a fine china plate and then gluing the fragments together; the outcome may look like a plate even though some pieces are probably not in the right place. 

We discussed this publication in our biweekly journal club - BioTalks.  We are interested in it because we study how human cells enter mitosis with damaged DNA.  It seems that some of the cells that survive this event (checkpoint adaptation) might be able to do so because they have reassembled broken chromosomes.

The reference for the paper is:
Stephens, PJ et al.  Cell 144: 27-40, 2011. 

The big paper is finally submitted

We have submitted a manuscript on our principle project.  This is the period of calm that lays between the rush to submit and the time before one receives comments from the reviewers.  The manuscript describes how human cancer cells undergo checkpoint adaptation:  a sort of  "double or nothing" cellular game in which cells will divide even though they have damaged DNA.  The manuscript connects the dots of hundreds of observations described in the literature where mitosis has been observed in cells treated with DNA damaging agents.  We have mapped this terrain in a systematic fashion.  We then go beyond mapping by proposing a mechanism to explain the steps to enter mitosis under these conditions.  The important bit is that once you have a good map you can plan where you should go next.
Please feel free to contact me for more information or for a preprint, while the calm lasts.

Science Education

February is shaping up to be education month.  Working in research has the additional benefit of highlighting areas of science education that need to be strengthened.  On 16 February I gave a lecture at the University of Calgary to students in the Cancer Biology course on the topic of Checkpoint Adaptation.  The textbook version states that cells with damaged DNA will die by apoptosis; everyone is surprised to learn that cells first enter mitosis and that some of these survive. 
This week I'm invited to participate in the Life Science Inspired Teaching Symposium in Toronto.  A leading Canadian science publisher is bringing scientists to the table to discuss the methods of teaching science.  One view is that students live is a noisy and distracting education world, we need to ensure that the science message gets their attention.  The month ends with another Checkpoint Adaptation lecture to the graduating biology class at the U of Lethbridge.  As usual, I will include a slide or two about Louis Pasteur. 

2012

A New Year
We had the pleasure of hosting a French stagiaire in the laboratory and we wish her luck with her studies back in France.  An undergraduate has moved onward to a co-op position after helping set up the video microscopy and winning 1st place in oral presentation of his work.  The video microscopy technique provided insight into the number of cells in population that undergo checkpoint adaptation.  The current team is now working on applying new techniques to measure enzyme activity and DNA damage in treated cancer cells so that we can predict better the mechanisms that drive checkpoint adaptation.

A new publication - Chk1 inhibitors

We have a second publication out this year.  This work is a major collaboration between chemists and biologists to find new chemical inhibitors of the enzyme Chk1.  The chemistry was led by Dr Françoise Perron-Sierra and Dr Patrick Casara; they developed a new method to modify an amazing class of compounds known as "indolocarbazoles".  By testing these new molecules we found several potent inhibitors of Chk1.  These compounds add to our arsenal of tools to study how cancer cells enter mitosis with damaged DNA.  The compounds also have potential as anti-cancer agents in solid tumours and leukaemias. 

If you have questions or would like to know more, feel free to contact either myself (roy.golsteyn@uleth.ca) or Françoise (francoise.perron-sierra@fr.netgrs.com).