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<p class="MsoNormal" align="center" style="text-align:center"><b><u><span lang="EN-US" style="font-size:26.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">JOB OPENING<o:p></o:p></span></u></b></p>
<p class="MsoNormal" align="center" style="text-align:center"><b><u><span lang="EN-US" style="font-size:26.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p><span style="text-decoration:none"> </span></o:p></span></u></b></p>
<p class="MsoNormal" align="center" style="text-align:center"><b><span lang="EN-US" style="font-size:22.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">Structural Bioinformatician (M/F) – PhD student position – 4 years<o:p></o:p></span></b></p>
<div style="mso-element:para-border-div;border:none;border-bottom:solid windowtext 1.0pt;padding:0cm 0cm 1.0pt 0cm">
<p class="MsoNormal" style="border:none;padding:0cm"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
</div>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">1. Description<o:p></o:p></span></p>
<p class="MsoNormal"><b><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">PhD student<o:p></o:p></span></b></p>
<p class="MsoNormal" style="text-align:justify;text-justify:inter-ideograph"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black">It is increasingly recognized that modulation of the immune system and inflammatory responses
by immune checkpoint regulators, such as co-stimulatory molecules, control cellular functioning in health and disease. Our laboratory has a long history in the investigation of the role of co-stimulatory molecules in cardiovascular disease, including atherosclerosis
and obesity. </span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black">A recently obtained grant will further focus on the cell type specific regulation of immune checkpoint inhibitors, including CD40-CD40L interactions,
and the signaling intermediates involved, in order to design and test novel therapeutics.
</span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black">TRAF signaling is an essential step in the co-stimulatory signaling process through the TNF-receptor in response to the presence of several known ligands. Functional
CD40-TRAF signaling is known to have important contributions to development of a number of pathologies, including atherosclerosis and diabetes. You will use structural bioinformatics methods including virtual ligand screening to develop and optimize novel
small-compound based therapeutic strategies. You will use rational methods to select potential ligands that target TRAF isoforms which may eventually be developed into novel orally available drugs to treat atherosclerosis. Based on the information collected
in a previous project and based on functional studies of the same biological pathways also small compounds interfering with other targets in the same signaling pathway may be addressed. The compounds will be tested for their efficacy in
<i>in vitro</i> assays as well as several relevant mouse models. </span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black"><o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:18.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
<p class="MsoNormal"><b><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">Relevant papers<o:p></o:p></span></b></p>
<p class="MsoListParagraphCxSpFirst" style="text-indent:-18.0pt;mso-list:l0 level1 lfo1;text-autospace:none">
<![if !supportLists]><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif""><span style="mso-list:Ignore">-<span style="font:7.0pt "Times New Roman"">
</span></span></span><![endif]><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">Zarzycka B, Seijkens T, Nabuurs SB, Ritschel T, Grommes J, Soehnlein O, Schrijver R, van Tiel CM, Hackeng TM, Weber C, Giehler F, Kieser A, Lutgens E, Vriend
G, Nicolaes GA. </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/25622654"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:windowtext;text-decoration:none">Discovery of small molecule CD40-TRAF6 inhibitors.</span></a><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">
J Chem Inf Model. </span><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">2015 23;55:294-307.
<o:p></o:p></span></p>
<p class="MsoListParagraphCxSpLast" style="text-indent:-18.0pt;mso-list:l0 level1 lfo1;text-autospace:none">
<![if !supportLists]><span lang="DE" style="font-size:11.0pt;font-family:"Helvetica","sans-serif""><span style="mso-list:Ignore">-<span style="font:7.0pt "Times New Roman"">
</span></span></span><![endif]><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">Chatzigeorgiou A, Seijkens T, Zarzycka B, ……Nicolaes G, Chavakis T, Lutgens E.
</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/24492375"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:windowtext;text-decoration:none">Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin
resistance.</span></a><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">
</span><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">Proc Natl Acad Sci U S A. 2014; 111:2686-91.</span><span lang="DE" style="font-size:11.0pt;font-family:"Helvetica","sans-serif""><o:p></o:p></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
<p class="MsoNormal"><span style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">2. We ask<o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">For this four-year project (ERC Consolidator grant) we are searching for a PhD-student with a master degree in biomedical sciences, life sciences, medicinal
chemistry or biochemistry. Especially candidates with experience in structural bioinformatics, drug design and programming in a LINUX environment are requested to apply. We search a PhD-student who is fascinated by scientific research and innovation, motivated
and eager to learn, who can work methodically and accurately and who is a great team player and has great communication and presentation skills in English. The ideal candidate will combine in silico and in vitro experimentation. Considering a potential small
teaching opportunity, the ability to speak Dutch would be considered an advantage.<o:p></o:p></span></p>
<p class="MsoNormal"><i><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></i></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">3. Where…<o:p></o:p></span></p>
<p class="MsoNormal" style="text-align:justify;text-justify:inter-ideograph"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black">You will work in a multidisciplinary international team that focuses on the interplay between
the vessel wall, plasma proteins and immune cells. This team is embedded in the Department of Medical Biochemistry of the Academic Medical Center Amsterdam (Amsterdam), and Maastricht University (Maastricht). The candidate will first be stationed at the Maastricht
University, where you will work in the group of Dr. Gerry Nicolaes, expert in the development of small compounds. You will be trained in drug discovery, design and optimization under the direction of Dr. Gerry Nicolaes. Upon positive identification of novel
biologically active compounds, you will be actively involved in the functional characterisation of molecules via in vitro and in vivo assays at the Amsterdam department of Medical Biochemistry, working under the direction of Prof. Esther Lutgens.</span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:black">
<o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">4. We offer<o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#3E3E3E;mso-fareast-language:EN-US">You will be employed on the basis of a 36-hour week. Appointment is for four years. Your salary will depend on your
qualifications and experience (according to UMC-CAO).</span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif""><br>
<br>
</span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:14.0pt;font-family:"Helvetica","sans-serif";color:#AA263A">5. Contact details<o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">For more information please contact dr. G. Nicolaes (</span><a href="mailto:g.nicolaes@maastrichtuniversity.nl"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">g.nicolaes@maastrichtuniversity.nl</span></a><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif"">)
</span><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p></o:p></span></p>
<p class="MsoNormal"><span lang="EN-US" style="font-size:11.0pt;font-family:"Helvetica","sans-serif";color:#AA263A"><o:p> </o:p></span></p>
<p class="MsoNormal"><span style="font-size:11.0pt"><o:p> </o:p></span></p>
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