Maternal origins of developmental reproducibility
Mariela D. Petkova, Shawn C. Little, Feng Liu, and Thomas Gregor. Current Biology 24 (11): 1283–1288 (2014).
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Mariela D. Petkova, Shawn C. Little, Feng Liu, and Thomas Gregor. Current Biology 24 (11): 1283–1288 (2014).
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Dmitry Krotov, Julien O. Dubuis, Thomas Gregor, and William Bialek. PNAS 111 (10): 3683–3688 (2014).
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Hernan G. Garcia, Mikhail Tikhonov, Albert Lin and Thomas Gregor. Current Biology 23, 2140–2145 (2013).
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Laurent Abouchar, Mariela D. Petkova, Cynthia R. Steinhardt, and Thomas Gregor (2013). arXiv.org:1309.6273 [q-bio.TO].
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Julien O. Dubuis, Gasper Tkacik, Eric F. Wieschaus, Thomas Gregor and William Bialek, PNAS 110, 16301-16308 (2013).
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Shawn C. Little, Mikhail Tikhonov and Thomas Gregor, Cell 154, 789–800 (2013).
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Shawn C. Little and Thomas Gregor, Cell 153, 509-510 (2013).
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Feng Liu, Alexander H. Morrison and Thomas Gregor, PNAS 110: 6724–6729 (2013).
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Julien O. Dubuis, Reba Samanta and Thomas Gregor, Molecular Systems Biology 9: 639 (2013).
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Alexander H. Morrison, Martin Scheeler Julien O. Dubuis and Thomas Gregor, Cold Spring Harb Protoc. 2012(4): 398-406 (2012).
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Here is another idea for “Science pizza” or “Journal Club”:
I am fascinated by the idea of “motivation“. I have been struggling with it ever since I realized during high school that I should do something with my live intellectually. And unfortunately that struggle didn’t cease until I finally got my own lab. And who knows, maybe it will start again once I get tenure (because “What’s next?”). Maybe others of us have similar/different experiences and it would be interesting to share these. In any case, I think waiting with the final motivation boost until you get your own lab is a bit long, and maybe there are things one can do already at the level of “how a lab is run” in order to avoid such long periods of “thirst”.
Interestingly, I just found this little video clip here, which led me to write this post and propose some discussion: To what extend is academia “there” in auto-motivating its work force? or How can we improve it? Please watch at your leisure Dan Pink‘s talk, which illustrates the hidden truths behind what really motivates us at home and in the workplace, and then let me know what you think. Maybe we can start by drawing the parallels between the business model and the academic model and see where that leads us to.
And no, my fever did not come back, nor am I on crack right now, I mean it.
The advent of Drosophila melanogaster (fruit fly) as a model organism has transformed modern biology in the 20th century. A brief history of how Drosophila opened new ways of seeing genes and helped understand the construction and the functioning of organisms can be found in this short article by Alfonso Martinez Arias entitled “Drosophila melanogaster and the Development of Biology in the 20th Century“.
More to the point of our first paper, the experiments that earned Nüsslein-Volhard and Wieschaus their Nobel prize aimed to identify genes involved in the development of Drosophila melanogaster embryos. At this point (the late 1970s and early 1980s) little was known about the genetic and molecular mechanisms by which multicellular organisms develop from single cells to morphologically complex forms during embryogenesis.
Fruit flies have long been an important model organism in genetics due to their small size and quick generation time, which makes even large numbers of them relatively easy to maintain and observe in the laboratory. Nüsslein-Volhard and Wieschaus identified genes involved in embryonic development by a series of genetic screens. They generated random mutations in fruit flies using a chemical. Some of these mutations affected genes involved in the development of the embryo. Nüsslein-Volhard and Weischaus took advantage of the segmentedform of Drosophila larvae to address the logic of the genes controlling development. In normal unmutated Drosophila, each segment produces bristles called denticles in a band arranged on the side of the segment closer to the head (the anterior). The researchers looked at the pattern of segments and denticles in each mutant under the microscope, and were therefore able to work out that particular genes were involved in different processes during development based on their differing mutant phenotypes (such as fewer segments, gaps in the normal segment pattern, and alterations in the patterns of denticles on the segments). Many of these genes were given descriptive names based on the appearance of the mutant larvae, such as hedgehog, gurken (German: “cucumbers”), and Krüppel ( “cripple”). Later, researchers identified exactly which gene had been affected by each mutation, thereby identifying a set of genes crucial for Drosophila embryogenesis. The subsequent study of these mutants and their interactions led to important new insights into early Drosophiladevelopment, especially the mechanisms that underlie the step-wise development of body segments.
These experiments are not only distinguished by their sheer scale (with the methods available at the time, they involved an enormous workload), but more importantly by their significance for organisms other than fruit flies. It was later found that many of the genes identified here had homologues in other species. In particular, the homeobox genes (coding for transcription factors critically involved in early body development) are found in all metazoans, and usually have similar roles in body segmentation.
These findings have also led to important realizations about evolution – for example, that protostomes and deuterostomes are likely to have had a relatively well-developed common ancestor with a much more complex body plan than had been conventionally thought. Additionally, they greatly increased our understanding of the regulation of transcription, as well as cell fate during development.
Here is a preparation of the cuticle from a Drosophila embryo, similar to those examined by Nüsslein-Volhard. Note the bands of denticles on the left hand side (towards the head) of each segment:
Source: Wikipedia
Some of us are watching this here tomorrow at 11am on Bob’s mega screen:
http://www.leica-microsystems.com/superres
Science pizza right after that (noon) there.
PLoS Press Release for our first paper on mRNA quantification in whole embryos.
“How are biologic molecules arranged inside the embryo so that embryonic development occurs reliably every time? Princeton researchers, led by Thomas Gregor, an assistant professor of physics and the Lewis-Sigler Institute for Integrative Genomics, and Shawn Little, a postdoctoral fellow in the laboratory of Professor Eric Wieschaus in the Department of Molecular Biology, have developed a new method to better understand how an embryo’s basic molecular makeup helps ensure that the embryo’s development occurs reliably every time. The results of this research into the fruit fly Drosophila introduce a method for making precise measurements of biologic units (so-called mRNA molecules) that play a key role in development. The findings are published in the March 1st issue of in the online, open access journal PLoS Biology.”
Shawn Little, Gašper Tkačik, Thomas Kneeland, Eric Wieschaus and Thomas Gregor, PLoS Biology 9(3): e1000596 (2011).
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Pankaj Mehta and Thomas Gregor, Current Opinion in Genetics & Development 20, 574-80 (2010).
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If you’re new to science and are curious to learn more about what our interests in the lab are, here are a couple of easy readings that professional science writers have written about our science. These pieces are meant to be accessible for everybody, no fancy science language nor any unnecessary jargon to pump up the jam…
Here is one on our amoebae work:
Scientists discover the molecular heart of collective behavior
And here is one on our fly work:
Fruit fly research may ‘clean up’ conventional impressions of biology
For other easy access writings please visit the media tab.
T. Gregor, K. Fujimoto, N. Masaki and S. Sawai, Science 328, 1021-1025 (2010).
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Here is a very nice feature on John Bonner, Princeton emeritus professor and Dictyostelium hero. With a standing activity of over 70 years of research, he is probably the longest living research contributor to the fascinating world of the social amoebae.
He discovered in 1947 that Dictyostelium cells are attracted by and chemotax towards a chemical called cyclic adenosine monophosphate or cAMP. And it is only now, more than 60 years later that we can actually visualize and measure the concentration of this chemical in living Dictyostelium cells using an optical technology called FRET.
This is a sampler of Bonner’s outstanding movie collection that he started during his undergraduate days:
If you want to read more on him please go here.
Even if people can always apply by simply sending me an email, for the next two months I am actually officially looking to fill a postdoctoral position, primarily to work on the fly embryogenesis project. It would make some administrators at Princeton really happy if you could go through this site and follow instructions from there. Please be sure to clearly state why you would be interested in joining the lab.