<div class="gmail_quote">--<br>
Venkataramanan Soundararajan, PhD<br>
Postdoctoral Associate, Harvard-MIT Division of Health Sciences & Technology<br>
Massachusetts Institute of Technology, Cambridge, MA 02139<br>
Website -- <a href="http://web.mit.edu/venk/www" target="_blank">http://web.mit.edu/venk/www</a><br>
<br>
<br>
IAP and Spring 2011<br>
Multiple Openings<br>
UROP Department/Lab/Center: Harvard-MIT Division of Health Sciences and<br>
Technology (HST)and MIT Biological Engineering (BE)<br>
Faculty Supervisor: Prof. Ram Sasisekharan<br>
<br>
Project #1<br>
Project Title: A Novel Approach to Structure-based Protein Design and<br>
Engineering<br>
<br>
Project Description: The rational design of proteins is central to the<br>
engineering of novel molecules for a broad-spectrum of biotechnology and medical<br>
applications. However, design-based protein engineering has been rife with<br>
challenges arising from misfolding, instability, and dysfunction of the<br>
designed molecules. In recent years, our group has been actively decoding the<br>
rules governing folding, stability, and function for diverse human and pathogen<br>
proteins, owing to our development of powerful in-house structural and sequence<br>
analysis tools (e.g. see our recent publications in Nature Biotechnology 2009<br>
and PLoS ONE 2010 at the following links --<br>
<a href="http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html" target="_blank">http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html</a> and<br>
<a href="http://dx.plos.org/10.1371/journal.pone.0009391" target="_blank">http://dx.plos.org/10.1371/journal.pone.0009391</a>). Towards furthering the<br>
decoding of rules governing design-based protein engineering and applying such<br>
knowledge for creating novel proteins with important therapeutic applications,<br>
we are currently seeking an undergraduate student with keen interest in both<br>
the computational and experimental aspects of molecular structural biology.<br>
Specifically, this UROP is ideally suited for students with interest in both<br>
(i.) learning state-of-the-art molecular modeling (e.g. Discovery Studio,<br>
PyMol) and programming (e.g. MATLAB) tools for the de novo design of novel<br>
proteins; and (ii.) performing guided bench work for experimental validation of<br>
the designed protein's functions. The UROP student will benefit from working<br>
with senior researchers in a fast-paced group and is expected to co-author<br>
significant journal publications emerging from this research (as has been the<br>
norm with all of our past and present UROPs). The UROP engagement is expected<br>
to commence during the IAP/Spring 2011 term, or earlier if a suitable candidate<br>
expresses interest.<br>
<br>
Prerequisites: Strong analytical abilities and an active interest in<br>
computational/molecular biology are both desirable skills for this UROP<br>
research.<br>
<br>
Contact: Dr. Venky Soundararajan (<a href="http://web.mit.edu/venk/www/" target="_blank">http://web.mit.edu/venk/www/</a>) by e-mail at<br>
<a href="mailto:venk@mit.edu">venk@mit.edu</a><br>
<br>
<br>
Project #2<br>
Project Title: Engineering a Database of Virus Surface Protein Molecular Models<br>
to Decode Patterns of Antigenic and Functional Site Evolution towards<br>
Developing Novel Therapeutic Solutions<br>
<br>
Project Description: This UROP will involve the use of in-house molecular<br>
modeling tools to compute a database of viral surface protein molecular<br>
structures from NCBI bioinformatics databases. The main goal of this<br>
constructed massive database will be to develop protocols for analysis and<br>
mining of novel biomedical signatures that will facilitate important biomedical<br>
and biotechnological applications. Specifically for influenza virus, the<br>
determinants of (i.) glycan receptor-binding specificity of viral hemagglutinin<br>
protein and (ii.) antigenic evolution; will be determined by utilizing<br>
techniques from our recently published studies (see our Innate Immunity 2010<br>
and Nature Biotechnology 2009 papers at the following links --<br>
<a href="http://ini.sagepub.com/content/early/2010/08/09/1753425910377099.abstract" target="_blank">http://ini.sagepub.com/content/early/2010/08/09/1753425910377099.abstract</a> and<br>
<a href="http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html" target="_blank">http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html</a> ). Significant<br>
biological and therapeutic value is anticipated for the results emerging this<br>
analysis, which is expected to lead to important scientific publications. The<br>
UROP engagement is expected to commence during the IAP/Spring 2011 term, or<br>
earlier if a suitable candidate expresses interest.<br>
<br>
Prerequisites: Strong analytical abilities, with an active interest in database<br>
construction and data mining, are desirable for this UROP research.<br>
<br>
Contact: Dr. Venky Soundararajan (<a href="http://web.mit.edu/venk/www/" target="_blank">http://web.mit.edu/venk/www/</a>) by e-mail at<br>
<a href="mailto:venk@mit.edu">venk@mit.edu</a><br>
<br>
Project #3<br>
Project Title: Construction of a Universal Protein Sequence-to-Structure<br>
Database for High-throughput Mining of Structure-Function Relationships<br>
<br>
Project Description: This UROP research will commence with building on the<br>
in-house, high-throughput sequence-to-structure mapping protocol developed<br>
recently by our group published in PLoS ONE and Innate Immunity<br>
(<a href="http://dx.plos.org/10.1371/journal.pone.0009391" target="_blank">http://dx.plos.org/10.1371/journal.pone.0009391</a> and<br>
<a href="http://ini.sagepub.com/content/early/2010/08/09/1753425910377099.abstract" target="_blank">http://ini.sagepub.com/content/early/2010/08/09/1753425910377099.abstract</a>), to<br>
enable the construction of a universal protein structural database. Post<br>
construction of the database, an appropriate Graphical User Interface (GUI) is<br>
to be developed, to showcase the bioinformatics information content relating to<br>
the modeled protein structures. Our vision is to create an easy-to-mine database<br>
of the universal set of molecular models built, using which resource, specific<br>
biological applications such as sequence-to-function mapping will be explored.<br>
There is a rich plethora of protocols already implemented by our past and<br>
present UROPs, and the new UROP is expected to quickly adapt to working with<br>
our group to further these goals. Based on the interests of the UROP, several<br>
follow-up applications may be explored, in the post-database-construction<br>
phase, including de novo identification of glycan-binding properties from amino<br>
acid sequence. This project will involve significant analytical and<br>
computational skills. Journal publications are already being compiled and it is<br>
expected that this UROP student will contribute to these papers as a co-author.<br>
The UROP engagement is expected to commence during the IAP/Spring 2011 term, or<br>
earlier if a suitable candidate expresses interest.<br>
<br>
Prerequisites: Strong analytical abilities, with a vivid and creative<br>
imagination, general appreciation of structures/geometry, and an active<br>
interest in molecular modeling and computational biology are all desirable<br>
traits for this UROP research.<br>
<br>
Contact: Dr. Venky Soundararajan (<a href="http://web.mit.edu/venk/www/" target="_blank">http://web.mit.edu/venk/www/</a>) by e-mail at<br>
<a href="mailto:venk@mit.edu">venk@mit.edu</a><br>
<br>
<br>
Project #4<br>
Project Title: Pattern Recognition on Protein Structural Surfaces: Applications<br>
to Decode the Glycosylation Machinery<br>
<br>
Project Description: This UROP is a very fundamental biological project with<br>
broad applications that are expected to provide significant insight into the<br>
biomolecular mechanisms facilitating the glycosylation of proteins.<br>
Glycosylation is one of the most common post-translational modifications and is<br>
performed by numerous enzymes with poorly defined specificity. The goal of this<br>
UROP is to build on the in-house protein structural analysis protocols<br>
developed by us recently (e.g. see our recent publications in Nature<br>
Biotechnology 2009 and PLoS ONE 2010 at the following links --<br>
<a href="http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html" target="_blank">http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html</a> and<br>
<a href="http://dx.plos.org/10.1371/journal.pone.0009391" target="_blank">http://dx.plos.org/10.1371/journal.pone.0009391</a> ) for recognition of 'signature<br>
glycosylation patterns' on the molecular surfaces of diverse protein<br>
structures. The findings that emerge from this analysis are expected to have<br>
major implications for furthering our understanding of the glycosylation<br>
machinery, thus opening the doors for novel biotechnological applications<br>
involving prediction and modulation of these fundamental processes. If<br>
successful, similar protocols may be more broadly explored for predicting<br>
signatures of other biologically and biomedically important post-translational<br>
modifications, as well. The advances enabled by this UROP study are expected to<br>
result in major publications in pioneering journals that will have a profound<br>
impact on molecular biology at large.<br>
<br>
Prerequisites: Strong analytical abilities with some previous MATLAB experience<br>
is desirable for this UROP research.<br>
<br>
Contact: Dr. Venky Soundararajan (<a href="http://web.mit.edu/venk/www/" target="_blank">http://web.mit.edu/venk/www/</a>) by e-mail at<br>
<a href="mailto:venk@mit.edu">venk@mit.edu</a><br>
<br>
Project #5<br>
Project Title: Mining Protein-Protein Interfaces for Understanding Biomolecular<br>
Interaction Specificity and Furthering Design-based Therapeutic Engineering<br>
<br>
Project Description: This UROP research involves the development of a protocol<br>
for mining of protein-protein interfaces from the PDB, by building on our<br>
recently-showcased and novel protein structural analysis tools (e.g. see our<br>
recent publications in Nature Biotechnology 2009 and PLoS ONE 2010 at the<br>
following links --<br>
<a href="http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html" target="_blank">http://www.nature.com/nbt/journal/v27/n6/full/nbt0609-510.html</a> and<br>
<a href="http://dx.plos.org/10.1371/journal.pone.0009391" target="_blank">http://dx.plos.org/10.1371/journal.pone.0009391</a> ). The goal is to compute the<br>
signatures of protein-protein interaction specificity and affinity. Novel<br>
analytical approaches have been envisioned to enable the mining and analysis<br>
aspects of this research. The ideal UROP student would have an inherent ability<br>
to recognize patterns from analysis of data-rich signals. Prediction of<br>
protein-protein interactions is a significant biological advancement with major<br>
biotechnological implications. Important scientific and technological<br>
publications are hence expected from this UROP research.<br>
<br>
Prerequisites: Strong analytical abilities with some previous MATLAB experience<br>
is desirable for this UROP research.<br>
<br>
Contact: Dr. Venky Soundararajan (<a href="http://web.mit.edu/venk/www/" target="_blank">http://web.mit.edu/venk/www/</a>) by e-mail at<br>
<a href="mailto:venk@mit.edu">venk@mit.edu</a><br>
<br>
</div><br>