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Students Win Biotechnology Awards at State Science Fair

Saturday, March 29, 2014  
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Virginia Bio, in conjunction with the Virginia Bio Foundation, presented awards at the 2014 Virginia State Science and Engineering Fair on Saturday, March 29, 2014, at Virginia Military Institute in Lexington. The volunteer judges studied the abstracts prior to their arrival at the Fair and then voted on the top projects to interview one-on-one at the event.

"It was hard to choose among so many outstanding projects," said Jeffrey Gallagher, Virginia Bio CEO. “The judges were extremely impressed by the caliber of the work.”

After talking with each of the students, the judges made their final selections:

First Place: Tina Ju, Senior, Thomas Jefferson High School for Science and Technology
Project Title: Discovery and engineering of exceptionally potent biological inhibitors of MERS-CoV and influenza H7N9
Abstract: A new virus, the Middle East Respiratory Syndrome CoronaVirus (MERS-CoV), and a new strain of avian influenza, H7N9, were recently isolated. They infect humans with high mortality (44% and 22%, respectively) and have pandemic potential, posing significant threats to health, security and economy. There are no effective therapeutics. Here, I present two interrelated projects: (1) the discovery of highly effective human monoclonal antibodies against MERS-CoV, completed; and (2) the engineering of a  novel class of antibody-peptide fusion proteins against influenza H7N9, ongoing. To select specific, high- affinity antibodies, we panned a large, naive phage-displayed human antibody library using the envelope glycoproteins of each virus. We have discovered three fully human monoclonal antibodies (mAbs)  against the MERS-CoV receptor binding domain (RBD) and one to the H7N9 hemagglutinin 1 (HA1). The MERS-CoV-specific mAbs bound with very high (subnanomolar) avidity to the RBD and neutralized pseudovirus and live virus with exceptional potency (50% neutralization (IC50) equal to 0.01 and 0.07 µg/ml, respectively) and are being tested in an animal model. The HA1-specific mAb bound with high (nanomolar) avidity to the HA1 and neutralized H7N9 with modest potency (IC50 = 25 µg/ml). To  increase the potency of the newly discovered mAbs they were fused through linkers to inhibitory peptides targeting membrane fusion intermediates during virus entry. These engineered bispecific fusion proteins are being expressed and tested for their inhibitory activity. The newly discovered mAbs and their derivative engineered fusion proteins will be further developed for the prophylaxis and therapy of infections in humans.

Second Place: Andrea Li
, Junior, Thomas Jefferson High School for Science and Technology
Project Title: Engineering a Novel Purification Approach for Stem Cell Therapies of Degenerative Eye Diseases through Surface Proteome Analysis
Abstract: In recent years, advances in stem cell technology have introduced the possibility for treatment of degenerative diseases. For example, in age-related macular degeneration (AMD), replacement of the retinal pigment epithelium (RPE) could restore vision and cure this currently untreatable disease. However, whether in embryonic stem cells or induced pluripotent stem cells (iPSCs) reprogrammed from easily accessible sources such as the skin, differentiation efficiency is never 100%. A purification step is therefore critical in isolating pure populations for effective disease modeling and drug screening, and in preventing tumor formation following cell replacement therapy. Because current purification methods are problematic, this project seeks to use a novel surface biomarker approach for efficient purification of iPSC-derived RPE cells for AMD treatment. In this project's first phase, computational bioinformatics techniques analyzed 1,882 RPE surface proteins to filter for 26 of particular interest. In the second phase, these 26 proteins were further investigated using immunofluorescence and western blotting to yield a better understanding of these proteins on a cellular level. Ultimately, a canonical set  of five RPE surface biomarkers will enable automated purification of iPSC-derived RPE cells via magnetic- activated cell sorting. These purified cells can later be tested for proper functionality and grown on scaffolds for transplantation into AMD patients. Furthermore, as a proof of concept experiment, this project outlines a generalized methodology through which purification of stem cell therapies for other cell types may be automated for more effective disease modeling, drug screening, and translation into the clinical setting for treatment of degenerative diseases.

Third Place: Caitlin Dutta, Western Albemarle High School
Project Title: The Effect of a New Long Non Coding Rna 2953 on Muscle Creation
Abstract: Long non-coding RNAs could become a revolutionary treatment for people with muscle ailments if they could be inserted into patients. In previous years, I studied the ability of certain microRNAs to induce differentiation in C2C12 mouse muscle cells. This year, I studied lncRNA 2953. lncRNA 2953 is significantly upregulated during muscle differentiation but little is known about its function. I studied the transcript of lncRNA 2953 by chromatin walking. I expanded the transcript by 1600bp and found that there are several splicing junctions, and contains no open reading frames. I analyzed lncRNA 2953's function by comparing C2C12 cells transfected with si2953 to cells transfected with a negative control. I did QPCR for Myosin Heavy Chain, Myogenin, miR-133b, Mef2c, and lncRNA linc-MD1. All of these molecules are positively associated with muscle differentiation. In cells transfected and grown in differentiation medium, I found that the knockdown of lncRNA 2953 increased the levels of these factors implying that knockdown accelerates differentiation. Additionally, I did immunofluorescence for MHC. I found that there was increased cell fusion and MHC levels in knockdown cells than in control cells. I also ran experiments for cells forced into differentiation by high density that stopped cell proliferation. I found that in differentiation caused this way, knockdown of lncRNA 2953 did not have much of an effect. This means that lncRNA's actions are prompted by decreased growth factors, not a halting of cell proliferation. With further work, lncRNA 2953 could become a great treatment.

Honorable Mentions:

Eryney Marrogi
Project Title: Develop an Assay Based on Peptide Pull-down to Screen Chemical Inhibitors Blocking the Binding of Kat2B to Acetylated Histone Tail

Rachel Zoll
Project Title: Growth and Characterization of periodically oriented GAN for Non-Linear Optics

Xioran Zhu
Project Title: A Portable Nasal Spirometer:  Diagnosing and Monitoring Pulmonary diseases

Lillian Xu
Project Title: Discovery of a Novel Genetic Cause of Atherosclerosis:  Foam Cell Differentiation

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