Team:KULeuven/Model/Cell Death

From 2008.igem.org

Revision as of 09:15, 30 July 2008 by Maarten (Talk | contribs)

Result:

To have a dropdown for your own team copy over all of the content below. It might be needed to adjust a thing or two. Comments have been added throughout the code what must be changed.

Inspirational websites:

  • [http://javascript-array.com/scripts/simple_drop_down_menu/ Most basic dropdown menu, with no submenu's]
  • [http://jquery.com/ The javascript library used to add effects and optimise the dropdown]
  • [http://www.tyssendesign.com.au/articles/css/centering-a-dropdown-menu/ How to center a ul list effectively]

The dropdown has been created and developed by the KULeuven team. 

<html>

<style type="text/css">
#content {z-index:4;}
#ddwrapper * {z-index:8 !important;}

div#ddwrapper {
	margin:0;
	padding:0;
	height:28px;
	width:945px;				/* change to adjust imperfections in width */
}
div#ddnav {
	margin:0 auto;				/* needed to center the dropdown */
	padding:0;
	top:5px;
	/* width: 965px */
	visibility:hidden;			/* dropdown is hidden until properly initalised by javascript */
}
div#ddtoggle {
	margin:0;
	position:fixed;
	right:2px;
	top:15px;
	height:10px;
	width:10px;
	z-index:100;
}

#ddnav ul {
	display:table-row;			/* works only for firefox, later adjusted by javascript for IE */
	margin:0 auto;
	padding:0;
}
#ddnav ul li {
	display:table-cell;			/* works only for firefox, later adjusted by javascript for IE */
	list-style:none;
	margin:0;
	padding:0 !important;
	border-right:1px solid #FFF;		/* creates illusion of spacing between tabs */
}
#ddnav ul li:last-child{border-right:none;}
#ddnav a{
	display:block;
	margin:0;
	padding:4px 14px;			/* play with dimensions for size of tabs */
	background-color:#075A90;		/* background color for tabs */
	color:#FFF !important;			/* font color for text in tabs */
	text-align:center;			/* aligning for text in tabs */
	text-decoration:none !important;
	font:bold 10pt Trebuchet MS;		/* font properties for text in tabs */
	outline:0;
}
#ddnav ul li a:hover {background-color:#99CCFF;}/* background color for tabs on mouseover */
#ddnav li a:active {outline:none;}		/* remove standard dotted border for links when clicked (IE) */
#ddnav li a:focus {-moz-outline-style:none;}	/* remove standard dotted border for links when clicked (FF) */
#ddnav div {
	display:none;
	position:absolute;
	width:9em;
	background-color:#000;			/* bug solution, do not change ! */
	border:1px solid #5970B2;		/* border color for dropdown menus */
	opacity:0.9;				/* transparancy of the dropdown menus (FF) */
	filter:alpha(opacity=90);		/* transparancy of the dropdown menus (IE) */
}
#ddnav div a {
	display:block;
	padding:5px 10px;			/* play with dimensions of block element in dropdown menus */
	position:relative;
	font:normal 8pt arial;			/* font properties for text in dropdown menus */
	text-align:left;			/* aligning of text in dropdown menus */
	cursor:pointer;
}
#ddnav div a:hover, #ddnav span a:hover {color:#000 !important;}	/* text color on mouseover */
#ddnav span div {
	position:relative;
	border:none;
	border-bottom:2px groove #5970B2;	/* separator for submenus, groove does not work in FF */
	opacity:1.0;				/* avoid stacking transparancy for submenus (FF) */
	filter:alpha(opacity=100);		/* avoid stacking transparancy for submenus (IE) */
}

/* may want to upload the following pictures to a new location */
.expand {background: url('https://static.igem.org/mediawiki/2008/e/ef/Icon-expand.png') no-repeat 95% 50%;}
.collapse {background: url('https://static.igem.org/mediawiki/2008/c/cd/Icon-collapse.png') no-repeat 95% 50%;}

.docked {background: #99ccff url("https://static.igem.org/mediawiki/2008/6/62/Ddnavundock.png") no-repeat 50% 50%;}
.undocked {background: #99ccff url("https://static.igem.org/mediawiki/2008/e/e4/Ddnavdock.png") no-repeat 50% 50%;}
</style>

<!-- IMPORTANT: save following script under a personalized webspace or download the library at www.jquery.com -->
<script type="text/javascript" src="http://student.kuleuven.be/~s0173901/wiki/js/jquery.js"></script>
<script type="text/javascript">
	function ddnav() {
		$('#ddnav ul li').hover(
			function () {
				$(this).find('div:first').css('display','block');},
			function () {
				$(this).find('div:first').css('display','none');}
		);
	}
			
	function ddnavsub() {
		$('#ddnav span > a').toggle(
			function () {
				$(this).removeClass("#ddnav expand").addClass("#ddnav collapse");
				$(this).parent().find('div:first').slideDown('fast');
				$(this).hover(
					function (){$(this).css('background-color','#99AAFF');},
					function (){$(this).css('background-color','#99AAFF');});},
			function () {
				$(this).removeClass("#ddnav collapse").addClass("#ddnav expand");
				$(this).parent().find('div:first').css('display','none');
				$(this).hover(
					function (){$(this).css('background-color','#99CCFF');},
					function (){$(this).css('background-color','#075A90');});}
		).addClass("#ddnav expand");
	}
	
	/* If you wish to omit the docking feature, remove following function ddtoggle() */	
	function ddtoggle() {
		$('#ddtoggle').toggle(
			function () {
				$(this).removeClass('undocked').addClass('docked');
				$('#ddnav').css('position','fixed');},
			function () {
				$(this).removeClass('docked').addClass('undocked');
				$('#ddnav').css('position','static');}
		);
	}

	function ddalign() {
		var _windowWidth = $(window).width();
		var _leftOffset = (_windowWidth - 965)/2;

		$('div#ddnav').css('left',_leftOffset);
	}
			
	function ddmsie() {
		$('#ddnav a').hover(
			function () {$(this).css('background-color','#99ccff');},
			function () {$(this).css('background-color','#075a90');}
		);
				
		/* toggle doesn't work yet */
		$('#ddtoggle').css('display','none');
				
		$('#ddnav ul').css('display','inline-block');
		$('#ddnav ul li').css('display','inline');
		$('#ddnav ul li').css('position','relative');
		$('#ddnav ul li>a').css('display','inline-block');
		$('#ddnav ul li>a').css('margin-right','-4px');
				
		$('#ddnav div').css('left','0');
		$('#ddnav div').css('top','100%');
		$('#ddnav span div').css('top','0');
	}
			
	function ddmozilla() {
		ddtoggle();
		$(window).bind('resize', function() {ddalign();});
	}

	$(function () {
		ddnav();
		ddnavsub();

		if(jQuery.browser.msie) ddmsie();
		if(jQuery.browser.mozilla) ddmozilla();

		$('#ddnav').css('visibility','visible');
	});
</script>

<!-- If you wish to omit the docking feature omit following line (div with id ddtoggle) -->
<div id="ddtoggle" class="undocked"></div>
<div id="ddwrapper">
<!-- Here the actual links are defined, simply replace with your own links in the appropriate sections -->
<div id="ddnav" align="center">
<ul>
	<li>
		<a href="https://2008.igem.org/Team:KULeuven">Home</a>
	</li>
	<li>
		<a>The Team</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Team/LabsandGroups">Research Labs and Groups</a>
			<a href="https://2008.igem.org/Team:KULeuven/Team/Students">Students</a>
			<a href="https://2008.igem.org/Team:KULeuven/Team/Instructors">Instructors</a>
			<a href="https://2008.igem.org/Team:KULeuven/Team/Advisors">Advisors</a>
                        <a href="https://2008.igem.org/Team:KULeuven/Team/Pictures">Pictures</a>
		</div>
	</li>
	<li>
		<a>The Project</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Project">Summary</a>
			<span>
				<a>Components</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Input">Input</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Output">Output</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Filter">Filter</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Inverter">Invertimer</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Reset">Reset</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/CellDeath">Cell Death</a>
					<a href="https://2008.igem.org/Team:KULeuven/Project/Memory">Memory</a>
				</div>
			</span>
                        <a href="https://2008.igem.org/Team:KULeuven/Evaluation">End Evaluation</a>
			<a href="https://2008.igem.org/Team:KULeuven/Literature">Literature</a>
                        <a href="https://2008.igem.org/Team:KULeuven/Brainstorm">Brainstorm</a>
		</div>
	</li>
        <li>
		<a>Ethics</a>
		<div>

		</div>
	</li>
	<li>
		<a>Submitted Parts</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Parts">Listing</a>
			<a href="http://partsregistry.org/cgi/partsdb/pgroup.cgi?pgroup=iGEM2008&group=KULeuven">Sandbox</a>
		</div>
	</li>
	<li>
		<a>Modeling</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Model/Overview">Overview</a>
			<a href="https://2008.igem.org/Team:KULeuven/Model/KineticConstants">Kinetic Constants</a>
			<span>
				<a>Components</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Model/Output">Output</a>
					<a href="https://2008.igem.org/Team:KULeuven/Model/Filter">Filter</a>
					<a href="https://2008.igem.org/Team:KULeuven/Model/Inverter">Invertimer</a>
					<a href="https://2008.igem.org/Team:KULeuven/Model/Reset">Reset</a>
					<a href="https://2008.igem.org/Team:KULeuven/Model/CellDeath">Cell Death</a>
					<a href="https://2008.igem.org/Team:KULeuven/Model/Memory">Memory</a>
				</div>
			</span>
			<a href="https://2008.igem.org/Team:KULeuven/Model/FullModel">Full Model</a>
                        <a href="https://2008.igem.org/Team:KULeuven/Model/Sensitivity">Sensitivity Analysis</a>
			<a href="https://2008.igem.org/Team:KULeuven/Model/MultiCell">Multi-cell Model</a>
			<a href="https://2008.igem.org/Team:KULeuven/Model/Diffusion">Diffusion</a>
		</div>
	</li>
	<li>
		<a>Data Analysis</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Data/Overview">Overview</a>
			<span>
				<a>New Parts</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Data/GFP">GFP (LVA-tag)</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/T7">T7 (UmuD-tag)</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Antisense">Antisense LuxI</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/ccdB">Celldeath (ccdB)</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/HybridProm">Hybrid Promotor</a>
				</div>
			</span>
                        <span>
				<a>Components</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Input">Input</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Output">Output</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Filter">Filter</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Inverter">Invertimer</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Reset">Reset</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/CellDeath">Cell Death</a>
					<a href="https://2008.igem.org/Team:KULeuven/Data/Memory">Memory</a>
				</div>
			</span>
			<a href="https://2008.igem.org/Team:KULeuven/Data/FullModel">Full Model</a>
		</div>
	</li>
        <li>
		<a>Software</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Software/MultiCell">Multi-cell Toolbox</a>
			<a href="https://2008.igem.org/Team:KULeuven/Software/Simbiology2LaTeX">Simbiology2LaTeX Toolbox</a>
		</div>
	</li>
	<li>
		<a>Notebook</a>
		<div>
			<a href="https://2008.igem.org/Team:KULeuven/Meeting_Calendar">Calendar</a>
                        <a href="https://2008.igem.org/Team:KULeuven/SummerHolidays">Summer Holidays</a>
			<span>
				<a>Reports</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Meeting Reports">Daily</a>
					<a href="https://2008.igem.org/Team:KULeuven/Weekly Meetings">Weekly</a>
				</div>
			</span>
			<span>
				<a>Lab Data</a>
				<div>
					<a href="https://2008.igem.org/Team:KULeuven/Freezer">Freezer</a>
					<a href="https://2008.igem.org/Team:KULeuven/Primers">Primers</a>
					<a href="https://2008.igem.org/Team:KULeuven/Ligation">Ligation</a>
				</div>
			</span>
			<a href="https://2008.igem.org/Team:KULeuven/Tools">Tools</a>
			<a href="https://2008.igem.org/Team:KULeuven/Press">Press</a>
			<a href="https://2008.igem.org/Team:KULeuven/Guestbook">Guestbook</a>
                        
		</div>
	</li>
        
</ul>
</div>
</div>
</html>
Pictogram celldeath.png

Contents

Cell Death

Position in the system

The Cell Death subsystem receives input from two other subsystems, namely:

LuxR is the component repressing the regulation of CcdB, the toxic product causing cell death. There the LuxR production is constitutive, no protein controls the gene regulation of LuxR, but the amount of LuxR available to repress the transcripion of the CcdB gene is controlled by HSL (Homoserine lactone).

If the inverter subsystem produces HSL (occurs when no light is detectable), this will forms a complex with LuxR. This will diminish the amount of LuxR available to repress the CcdB transcription and initiate cell death. When waiting long enough the amount of HSL becomes critical.

If however the pulse generator becomes active (by the filter), it will produce a pulse of lactonase, which will then bind to the HSL, reacting to an hydroxy-acid. As opposed to HSL, this hydroxy-acid will no longer form a complex with LuxR. This increase in LuxR lowers the CcdB production. The challenge is to generate a pulse of lactonase high enough to neutralise all HSL present in the cell.

Describing the system

Cell Death.jpg

ODE's

Parameters

Parameter values (Cell Death)
Name Value Comments Reference
Degradation Rates
dLuxR 0.0010 s-1
dLuxR_HSL 0.0010 s-1 complex of HSL and LuxR degrades, giving back HSL
dRNA_LuxR 0.00227 s-1 [http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=124983&blobtype=pdf link]
dCcdB 7.7E-5 s-1 [http://www.ncbi.nlm.nih.gov/pubmed/8022284?dopt=abstract link]
dRNA_CcdB 0.00231 s-1 [http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=124983&blobtype=pdf link]
dHSL 1.02E-6 s-1 [http://aem.asm.org/cgi/content/abstract/71/3/1291 link]
Association/Dissociation/Reaction Rates
kass (HSL+LuxR) 1E6 s-1 association rate of HSL with LuxR. Chosen to be relatively (to the other rate constants) high and such that Kdiss (HSL + LuxR) equals 10-6
kdiss (HSL+LuxR) 1 s-1 dissociation rate of the HSL-LuxR complex
kass (HSL+lactonase) 1E6 s-1 association rate of HSL with lactonase
kdiss (HSL+lactonase) 446.5 s-1 dissociation rate of the HSL-lactonase complex
kcat (HSL:hydroxy-acid) 29 s-1 catalytic transformation of HSL to an hydroxy-acid, lactonase is the enzyme [http://www.jbc.org/cgi/reprint/M311194200v1.pdf link]
Dissociation Constants
KHSL_LuxR 1E-6 [M]/L kdiss / kass (HSL+LuxR) [http://jb.asm.org/cgi/content/full/189/11/4127?view=long&pmid=17400743 link]
KHSL_LuxR 4.05E-6 [M]/L binding HSL_LuxR on LuxPromotor [http://parts.mit.edu/igem07/index.php/Tokyo/AHL_assay link]
Hill Cooperativity
nHSL_LuxR 2.08 [http://parts.mit.edu/igem07/index.php/Tokyo/AHL_assay link]
Transcription Rates
kmRNA_LuxR (constitutive promotor) 0.025 s-1 see Constitutive Promotors & E. coli transcription Rates
kmRNA_CcdB 0.025 s-1 maximal transcription rate for CcdB RNA (no LuxR repressor present)

[http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T39-3Y6HKD6-BK-1&_cdi=4941&_user=877992&_orig=search&_coverDate=08%2F30%2F1995&_sk=998379998&view=c&wchp=dGLbVtz-zSkzS&md5=49efd14150c71e668eabdef225220ce3&ie=/sdarticle.pdf This paper] says that synthesis of even a few molecules of the shorter CcdB protein is probably lethal.

Models

CellDesigner (SBML file)

Cell Death
Cell Death
Cell Death

Matlab

Retrieved from "http://2008.igem.org/Team:KULeuven/Model/Cell_Death"