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	<title>Laboratory for the Physics of Life</title>
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	<link>http://tglab.princeton.edu</link>
	<description>Thomas Gregor, Assistant Professor of Physics, Princeton University</description>
	<pubDate>Mon, 24 Aug 2009 02:24:51 +0000</pubDate>
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		<title>Postdoctoral position available</title>
		<link>http://tglab.princeton.edu/blog/postdoctoral-position-available/</link>
		<comments>http://tglab.princeton.edu/blog/postdoctoral-position-available/#comments</comments>
		<pubDate>Tue, 12 May 2009 23:52:27 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[Drosophila]]></category>

		<category><![CDATA[lab]]></category>

		<category><![CDATA[postdoctoral]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=588</guid>
		<description><![CDATA[
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 [...]]]></description>
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<p>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 <a title="Job offereing at jobs.phds.org" href="http://jobs.phds.org/job/13760/princeton-university/postdoctoral-position-in-physical-life-science" target="_blank">this site</a> and follow instructions from there. Please be sure to clearly state why you would be interested in joining the lab.</div>
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		<title>Lab construction completed</title>
		<link>http://tglab.princeton.edu/blog/lab-construction-completed/</link>
		<comments>http://tglab.princeton.edu/blog/lab-construction-completed/#comments</comments>
		<pubDate>Mon, 13 Apr 2009 12:26:36 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[construction]]></category>

		<category><![CDATA[Jadwin]]></category>

		<category><![CDATA[lab]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=509</guid>
		<description><![CDATA[And as of today, we have a laboratory in which we can start to do science, how exciting!
We have a large and a small optics room, great space to do bench work, an animal facility, 10 desks for students to sit and a newly renovated Departmental Chemistry and Biology facility. If you look closely you&#8217;ll [...]]]></description>
			<content:encoded><![CDATA[<p><a href="http://tglab.princeton.edu/blog/lab-construction-completed/" target="_self"><img class="alignright size-thumbnail wp-image-533" title="Lab entrance." src="http://tglab.princeton.edu/wp-content/uploads/2009/04/labcomplete5.jpg" alt="" width="112" height="150" /></a>And as of today, we have a laboratory in which we can start to do science, how exciting!</p>
<p>We have a large and a small optics room, great space to do bench work, an animal facility, 10 desks for students to sit and a newly renovated Departmental Chemistry and Biology facility. If you look closely you&#8217;ll even find real windows with a view outside in the real world, and that in a lab in the Physics Department. They didn&#8217;t put us in the basement!</p>
<p>Check it out..</p>
<p><span id="more-509"></span></p>

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		<title>Thomas will be speaking at these conferences this year:</title>
		<link>http://tglab.princeton.edu/blog/conference-presentations/</link>
		<comments>http://tglab.princeton.edu/blog/conference-presentations/#comments</comments>
		<pubDate>Wed, 11 Mar 2009 16:58:09 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[conference]]></category>

		<category><![CDATA[presentation]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=543</guid>
		<description><![CDATA[In March in Cambridge, UK at &#8220;Noise in Life 09&#8220;.
On April 25 at Harvard for the &#8220;Spring 2009 EPB Symposium&#8220;.
On April 30 at Princeton at the &#8220;Physical Principles in Biological Networks Program&#8221;
In May in Lisbon, Portugal at the workshop on &#8220;Biophysical Mechanism of Develoment&#8220;.
In August at Los Alamos at the &#8220;Third q-bio Conference on Cellular [...]]]></description>
			<content:encoded><![CDATA[<p>In March in Cambridge, UK at &#8220;<a title="Meeting website" href="http://www.cellsignet.org.uk/noise09/" target="_blank">Noise in Life 09</a>&#8220;.</p>
<p>On April 25 at Harvard for the &#8220;<a title="EPB website" href="http://www.physicalbiology.fas.harvard.edu/pages/description.html" target="_blank">Spring 2009 EPB Symposium</a>&#8220;.</p>
<p>On April 30 at Princeton at the &#8220;<a title="PDF of the Program" href="http://www.physics.princeton.edu/pcts/biological/ProgramBionet3-24.pdf" target="_blank">Physical Principles in Biological Networks Program</a>&#8221;</p>
<p>In May in Lisbon, Portugal at the workshop on &#8220;<a title="Workshop website" href="http://www.igc.gulbenkian.pt/workshopbmd/workshopbmd/workshopbmd/workshopbmd/index.html" target="_blank">Biophysical Mechanism of Develoment</a>&#8220;.</p>
<p>In August at <a title="Conference Website" href="http://cnls.lanl.gov/q-bio/index.html" target="_blank">Los Alamos</a> at the &#8220;<a title="Conference Wiki" href="http://cnls.lanl.gov/q-bio/wiki/index.php/The_Third_q-bio_Conference_on_Cellular_Information_Processing" target="_blank">Third q-bio Conference on Cellular Information Processing</a>&#8220;.</p>
<p>In September in Cambridge, UK (again) at the &#8220;<a title="Symposium website" href="http://www.gen.cam.ac.uk/plm/PLM4.html" target="_blank">4th Symposium on the Physics of Living matter</a>&#8220;.</p>
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		<title>Construction progress</title>
		<link>http://tglab.princeton.edu/blog/construction-progress/</link>
		<comments>http://tglab.princeton.edu/blog/construction-progress/#comments</comments>
		<pubDate>Sun, 08 Feb 2009 13:59:03 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[construction]]></category>

		<category><![CDATA[Jadwin]]></category>

		<category><![CDATA[lab]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=473</guid>
		<description><![CDATA[By the end of February things in the lab started to take shape&#8230;
]]></description>
			<content:encoded><![CDATA[<p>By the end of February things in the lab started to take shape&#8230;</p>

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		<title>Abstracts from contributions to recent international Dictyostelium meeting in Tsukuba/Japan</title>
		<link>http://tglab.princeton.edu/blog/dictyostelium-abstracts/</link>
		<comments>http://tglab.princeton.edu/blog/dictyostelium-abstracts/#comments</comments>
		<pubDate>Fri, 05 Dec 2008 05:22:13 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[adaptation]]></category>

		<category><![CDATA[amoeba]]></category>

		<category><![CDATA[Dictyostelium]]></category>

		<category><![CDATA[dynamics]]></category>

		<category><![CDATA[FRET]]></category>

		<category><![CDATA[input/output relation]]></category>

		<category><![CDATA[meeting]]></category>

		<category><![CDATA[modeling]]></category>

		<category><![CDATA[phase transition]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=317</guid>
		<description><![CDATA[Currently, I am in the process of finishing up my work on amoeba signaling and aggregation in Tokyo. This work is in collaboration with and in the laboratory of Satoshi Sawai at the University of Tokyo. We also collaborate with Koichi Fujimoto, a theorist at the same institution. While no papers have been published yet, [...]]]></description>
			<content:encoded><![CDATA[<p>Currently, I am in the process of finishing up my work on amoeba signaling and aggregation in Tokyo. This work is in collaboration with and in <a title="Japanese homepage of Sawai's laboratory" href="http://sawailab.c.u-tokyo.ac.jp/index.html" target="_blank">the laboratory of Satoshi Sawai</a> at the <a title="Univeristy of Tokyo homepage" href="http://www.u-tokyo.ac.jp/index_e.html" target="_blank">University of Tokyo</a>. We also collaborate with <a title="Koichi's homepage" href="http://chaos.c.u-tokyo.ac.jp/~fujimoto/" target="_blank">Koichi Fujimoto</a>, a theorist at the same institution. While no papers have been published yet, as a preview pasted below are <a title="view abstracts" href="http://tglab.princeton.edu/?p=317" target="_self">three abstracts</a> of contributions to a recent <a title="Dicty2008 conference" href="http://cosmos.bot.kyoto-u.ac.jp/dicty2008/index.html" target="_blank">international <em>Dictyostelium</em> meeting</a> held in Tsukuba/Japan. <span id="more-317"></span></p>
<h3>A phase transition to collective behavior in <em>Dictyostelium</em> cell populations</h3>
<p style="text-align: justify;">Collective dynamics are widely observed during development of multicellular bodies and emerge as a result of communication among individual cells via signaling molecules. However, little is known experimentally of the fundamental features that describe how the highly nonlinear spatio-temporal dynamics at the single-cell level can give rise to coherent dynamics at the population level. The prototypical example is cell-to-cell signaling among social amoebae <em>Dictyostelium</em>, where a few hundred thousand cells aggregate to form a fruiting body. cAMP is synthesized and secreted periodically and serves as a cue that directs chemotaxis of individual cells. <a title="Watch FRET-signal generating spiral waves in a layer of cells on agar." href="http://www.youtube.com/watch?v=uqi_WTllG7A" target="_blank">Here we use a FRET-based sensor protein, combined with live-imaging, to monitor cytosolic cAMP levels in developing <em>Dictyostelium</em> cells.</a> Single cell resolution timelapse recordings of cell populations during the first 10 hours of development reveal the very onset of periodic, spike-like signaling, as well as sequential changes in the signaling frequency. The input-output relation for wild-type and mutant strains obtained from single cells in isolation indicates that the intracellular cAMP dynamics is governed by a PI3kinase-TORC2-actin dependent feedback loop. Collective cAMP oscillations in populations of cells under perfusion reveal a sharp phase transition between a decoupled state and collective behavior for a range of cell densities and dilution rates. These observations together with a mathematical model that we have constructed, suggest that the intact population is able to drive itself to this transition spontaneously during development.</p>
<h3>Towards a quantitative input-output relationship in the <em>Dictyostelium</em> cAMP relay response</h3>
<p style="text-align: justify;">We revisit the input-output relationship between extracellular cAMP stimulus and intracellular response by live-cell imaging. <a title="Watch a single amoeba cell move in a perfusion chamber." href="http://www.youtube.com/watch?v=0v3pp8ZiwWU" target="_blank">Single <em>Dictyostelium </em>cells in isolation were stimulated via perfusion over extended periods of time (tens of minutes) with cAMP concentrations that range over 7 orders of magnitude.</a> Three typical response regimes are observed: 1) In the 10pM to 1nM range cells respond stochastically with a single cytosolic cAMP pulse that adapts perfectly on a fast ∼3 minute time scale. 2) In the 1nM to 1μM range cells also respond with a fast pulse but cytosolic cAMP continues to oscillate afterwards upon tonic stimulus. These internal oscillations have a damped behavior that is stimulus dependend, but the cells do not fully adapt. 3) In the 1μM-10μM range cytosolic cAMP concentration oscillates continuously but damping is no longer observed. Fourier power spectra for the internal cAMP oscillations reveal periods ranging from 2 to 6 minutes for applied concentrations of 10μM to 1nM, respectively. Damping ranges from minute- (100pM) to hour- (100nM) timescales. The input-output relationship, quantified by computing the concentration integral over the stimulated time interval, shows a sharp transition around 1nM. Furthermore, using a purified version of the sensor protein we estimate both the absolute cytosolic cAMP concentration as well as the number of molecules released by a single cell during a cAMP pulsation.</p>
<h3>Modeling adaptation and intrinsic cytosolic cAMP oscillations in isolated <em>Dictyostelium</em> cells</h3>
<p style="text-align: justify;">FRET-based measurements of cytosolic cAMP at the single-cell level have enabled us to reexamine the underlying biochemical pathways that give rise to the oscillations and waves of extracellular cAMP. Based on our recent live-cell imaging data from wildtype and mutant strains under various stimulus conditions, we propose a reaction-kinetics model that describes how ligand-binding to the receptor regulates ACA through multiple regulatory modules consisted of Ras, PI3K, TORC2 and F-actin. Our numerical and analytical studies show that a putative negative feedback regulation of F-actin/ACA is necessary to account for the sustained intracellular cAMP oscillations in cells under persistent stimulation. The key signature of the cAMP response that we have experimentally uncovered is the existence of two adaptation kinetics of distinct time-scales. Based on the model simulations, we suggest that the fast activation and adaptation of a cAMP response results from the regulation of PIP3 whereas the slow time scale adaptation derives from actin-dependent inhibition of ACA. By extending the single-cell studies to a multicellular context, we demonstrate that the putative negative feedback and the resulting intrinsic intracellular cAMP oscillations are essential for the onset of the extracellular cAMP oscillations at the population level.</p>
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		<title>Classic papers on signaling and aggregation of amoebae</title>
		<link>http://tglab.princeton.edu/blog/classic-papers/</link>
		<comments>http://tglab.princeton.edu/blog/classic-papers/#comments</comments>
		<pubDate>Fri, 21 Nov 2008 06:31:45 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Blog]]></category>

		<category><![CDATA[amoeba]]></category>

		<category><![CDATA[Dictyostelium]]></category>

		<category><![CDATA[references]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=292</guid>
		<description><![CDATA[Over the next few months/years I&#8217;d like to use this website to build up a repository of information on the various topics that we study in the lab. Today as a beginning I am introducing 4 classic papers that pioneered a system-level description and quantitative understanding of this spectacular phenomenon:

In this movie roughly 200 starved [...]]]></description>
			<content:encoded><![CDATA[<p>Over the next few months/years I&#8217;d like to use this website to build up a repository of information on the various topics that we study in the lab. Today as a beginning I am introducing <a title="view papers" href="http://tglab.princeton.edu/?p=292" target="_self">4 classic papers</a> that pioneered a system-level description and quantitative understanding of this spectacular phenomenon:</p>
<p><object classid="clsid:d27cdb6e-ae6d-11cf-96b8-444553540000" width="425" height="350" codebase="http://download.macromedia.com/pub/shockwave/cabs/flash/swflash.cab#version=6,0,40,0"><param name="src" value="http://www.youtube.com/v/hpHpBHJZQvU&amp;showsearch=0" /><embed type="application/x-shockwave-flash" width="425" height="350" src="http://www.youtube.com/v/hpHpBHJZQvU&amp;showsearch=0"></embed></object></p>
<p>In this movie roughly 200 starved amoebae of the species Dictyostelium discoideum are shown over 8 hours during which they find each other and culminate in a cellular slime mould. This process is seen as a survival strategy because individual amoebae would die under starvation whereas as in the multi-cellular organism 80% of the cells can survive as spores. <span id="more-292"></span></p>
<p>Here are 4 early papers that originally described the different aspects of this process:</p>
<ol>
<li>
<h4><a href="http://tglab.princeton.edu/wp-content/uploads/2008/11/the-american-naturalist-1957-shaffer.pdf">Aspects of Aggregation in Cellular Slime Moulds 1. Orientation and Chemotaxis</a></h4>
<p>The American Naturalist <strong>91</strong>, pp. 19-35 (1957)</li>
<li>
<h4><a href="http://tglab.princeton.edu/wp-content/uploads/2008/11/advances-in-cyclic-nucleotide-research-1972-konijn.pdf">Cyclic AMP as a first messenger</a></h4>
<p>TM Konijin, Advances in cyclic nucleotide research <strong>1,</strong> pp. 17-31 (1972)</li>
<li>
<h4><a title="Signal propagation during aggregation in the slime mould Dictyostelium discoideum" href="http://tglab.princeton.edu/wp-content/uploads/2008/11/j-gen-microbiol-1974-alcantara.pdf" target="_blank">Signal propagation during aggregation in the slime mould Dictyostelium discoideum</a></h4>
<p>J Gen Microbiol <strong>85</strong>, pp.321-34 (1974)</li>
<li>
<h4><a href="http://tglab.princeton.edu/wp-content/uploads/2008/11/eucaryotic-microbes-as-model-developmental-systems-1977-durston.pdf">The control of morphogenesis in Dictyostelium discoideum</a></h4>
<p>AJ Durston, in &#8220;Eucaryotic Microbes as Model Developmental Systems&#8221;, edited by O&#8217;Day DH, Horgen PA. New York: M. Dekker; pp. 294-321 (1977)</li>
</ol>
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		<title>General Introduction</title>
		<link>http://tglab.princeton.edu/researchblog/general-introduction/</link>
		<comments>http://tglab.princeton.edu/researchblog/general-introduction/#comments</comments>
		<pubDate>Mon, 17 Nov 2008 11:44:24 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Research]]></category>

		<category><![CDATA[biology]]></category>

		<category><![CDATA[introduction]]></category>

		<category><![CDATA[lab]]></category>

		<category><![CDATA[physics]]></category>

		<category><![CDATA[research]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=1</guid>
		<description><![CDATA[Traditionally, biological questions have been investigated with qualitative techniques that allow for interpretation classically in the context of evolution. This qualitative approach, however, struggles to adequately describe the dynamic nature of most of the essential biological processes upon which evolution is acting. Recent advances in molecular biology, optical microscopy, nanoscopic physics and computer science have [...]]]></description>
			<content:encoded><![CDATA[<p>Traditionally, biological questions have been investigated with qualitative techniques that allow for interpretation classically in the context of evolution. This qualitative approach, however, struggles to adequately describe the dynamic nature of most of the essential biological processes upon which evolution is acting. Recent advances in molecular biology, optical microscopy, nanoscopic physics and computer science have opened up new avenues for interpreting biological phenomena, combining high-precision measurement of biological processes with theoretical predictions and models that are bound by physical principles and formulated in mathematical language.  This allows for models to be numerically tested and validated by experiments and, conversely, for experiments to be designed and guided by theoretical models. My laboratory uses such an approach to understand a biological system holistically, within a framework of fundamental physical principles that dictate and constrain biological phenomena.</p>
<p>Research in the lab is highly interdisciplinary. The interests and expertise of the lab&#8217;s members range from physics to biology to computer science to engineering; we use a combination of computational and experimental approaches. We build microscopes and microfluidic devices to measure the concentrations dynamics of proteins and signaling molecules; we use tools from molecular biology and genetics to manipulate the organisms we study; and we use image analysis and modeling to analyze our data. Researchers are encouraged to move freely between the different disciplines and to learn a variety of techniques according to their specific needs and interests. We primarily address questions concerning the development of fruit fly embryos and emergent collective behavior via cell signaling in social amoeba populations, but we are open to new ideas and collaborations addressing questions in other model systems.</p>
]]></content:encoded>
			<wfw:commentRss>http://tglab.princeton.edu/researchblog/general-introduction/feed/</wfw:commentRss>
		</item>
		<item>
		<title>Introduction to early embryonic fruit fly development</title>
		<link>http://tglab.princeton.edu/researchblog/fruit-fly-related/</link>
		<comments>http://tglab.princeton.edu/researchblog/fruit-fly-related/#comments</comments>
		<pubDate>Sun, 16 Nov 2008 11:45:39 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Research]]></category>

		<category><![CDATA[biology]]></category>

		<category><![CDATA[development]]></category>

		<category><![CDATA[Drosophila]]></category>

		<category><![CDATA[embryo]]></category>

		<category><![CDATA[fruit fly]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=5</guid>
		<description><![CDATA[

&#8211;page under construction&#8211;
]]></description>
			<content:encoded><![CDATA[<p><object classid="clsid:d27cdb6e-ae6d-11cf-96b8-444553540000" width="425" height="344" codebase="http://download.macromedia.com/pub/shockwave/cabs/flash/swflash.cab#version=6,0,40,0"><param name="allowFullScreen" value="true" /><param name="allowscriptaccess" value="always" /><param name="src" value="http://www.youtube.com/v/j87y7EAj8qE&amp;showsearch=0&amp;hl=en&amp;fs=1" /><embed type="application/x-shockwave-flash" width="425" height="344" src="http://www.youtube.com/v/j87y7EAj8qE&amp;showsearch=0&amp;hl=en&amp;fs=1" allowscriptaccess="always" allowfullscreen="true"></embed></object></p>
<p><span id="more-5"></span></p>
<p style="text-align: center;"><strong>&#8211;page under construction&#8211;</strong></p>
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			<wfw:commentRss>http://tglab.princeton.edu/researchblog/fruit-fly-related/feed/</wfw:commentRss>
		</item>
		<item>
		<title>Introduction to social amoebae and their development</title>
		<link>http://tglab.princeton.edu/researchblog/amoebae-related/</link>
		<comments>http://tglab.princeton.edu/researchblog/amoebae-related/#comments</comments>
		<pubDate>Sat, 15 Nov 2008 11:49:21 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Research]]></category>

		<category><![CDATA[aggregation]]></category>

		<category><![CDATA[amoeba]]></category>

		<category><![CDATA[biology]]></category>

		<category><![CDATA[development]]></category>

		<category><![CDATA[Dictyostelium]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=7</guid>
		<description><![CDATA[

Information about my current research projects can be found here&#8230;
&#8211;page under construction&#8211;
]]></description>
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<p><span id="more-7"></span></p>
<p style="text-align: left;">Information about my current research projects can be found <a title="Meeting abstracts." href="http://tglab.princeton.edu/blog/dictyostelium-abstracts/" target="_self">here</a>&#8230;</p>
<p style="text-align: center;"><strong>&#8211;page under construction&#8211;</strong></p>
]]></content:encoded>
			<wfw:commentRss>http://tglab.princeton.edu/researchblog/amoebae-related/feed/</wfw:commentRss>
		</item>
		<item>
		<title>Introduction to early mammalian development</title>
		<link>http://tglab.princeton.edu/researchblog/mouse-related/</link>
		<comments>http://tglab.princeton.edu/researchblog/mouse-related/#comments</comments>
		<pubDate>Fri, 14 Nov 2008 10:01:15 +0000</pubDate>
		<dc:creator>Thomas Gregor</dc:creator>
		
		<category><![CDATA[Research]]></category>

		<category><![CDATA[biology]]></category>

		<category><![CDATA[development]]></category>

		<category><![CDATA[embryo]]></category>

		<category><![CDATA[in utero]]></category>

		<category><![CDATA[microscopy]]></category>

		<category><![CDATA[mouse]]></category>

		<guid isPermaLink="false">http://tglab.princeton.edu/?p=40</guid>
		<description><![CDATA[The laboratory is currently in the process to develop new in utero imaging techniques for early embryonic mouse development.

&#8211;page under construction&#8211;
]]></description>
			<content:encoded><![CDATA[<p>The laboratory is currently in the process to develop new <em>in utero</em> imaging techniques for early embryonic mouse development.</p>
<p><span id="more-40"></span></p>
<p style="text-align: center;"><strong>&#8211;page under construction&#8211;</strong></p>
]]></content:encoded>
			<wfw:commentRss>http://tglab.princeton.edu/researchblog/mouse-related/feed/</wfw:commentRss>
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