May 18, 2018 Mary Gates Hall

ties (both traditional and microcelebrities) are expected to be SESSION 1F evaluated as more credible than female celebrities. Third, tra- ditional male celebrities will be more credible than any other DELIBERATION,CREDIBILITY, AND kind of celebrity. Given credibility is deemed by scholars as a crucial component of persuasion, assessing microcelebrities’ THE RHETORICOF SCIENCE credibility provides a better understanding of their societal Session Moderator: Leah Ceccarelli, Communication and political mpact. MGH 234 12:30 PM to 2:15 PM ESSION * Note: Titles in order of presentation. S 1G

The Power of Microcelebrities: Difference in Perceived TOWARDS BETTER UNDERSTANDING Credibility between Male and Female Microcelebrities and Traditional Celebrities OF HUMAN DISEASESTHROUGH Brian Chan, Senior, Communication MOLECULAR BIOCHEMISTRY Mentor: Katy Pearce, Communication Session Moderator: Valerie Daggett, Bioengineering Mentor: Valerie Manusov, Communication MGH 238 Young people spend two-and-a-half as much time watch- 12:30 PM to 2:15 PM ing Internet videos as they do traditional television. Busi- * Note: Titles in order of presentation. ness concerns aside, questions remain about other effects of this change in media consumption. One such concern is of Design of an Alpha-Sheet for the Inhibition of celebrities and their influence. Research demonstrates that Aggregation in AL Amyloidosis celebrities are influential, in part because people consider Lauren Nicole Martini, Senior, Computer Engineering, them credible sources, even with regard to political infor- Bioengineering mation. Research also shows that a credible source is more Mary Gates Scholar effective at changing one’s attitude and behavioral intention Mentor: Valerie Daggett, Bioengineering than a low-credibility source. These research findings might Mentor: Matthew Childers, Bioengineering alter what was previously perceived as the influence of tra- The misfolding and aggregation of free light-chains into amy- ditional celebrities – movie stars, pop groups, and the enter- loid fibrils is the hallmark of antibody light-chain (AL) amy- tainment industry as a whole. With the growth of particu- loidosis, a fatal disease associated with the accumulation of lar participatory platforms and social media sites, a new type species in tissues throughout the body, including of celebrity exists: microcelebrity. Defined as an act of bol- the heart and kidneys. Current treatment options, including stering digital self-representation through media and technol- chemotherapy and bone marrow transplant, do not address ogy, the term microcelebrity has since evolved to include in- the causes of aggregation on a molecular level. Molecular dy- dividuals who construct self-representation and garner pop- namics (MD) simulations were used to investigate misfolding ularity online. Although there is a great deal of research pathways in the aggregation of two light chain monomers, Jto demonstrating that microcelebrities are also influential, es- and Wil. These simulations showed that under amyloidogenic pecially regarding consumer good purchases on social media, conditions, conversion from beta-sheet to alpha-sheet sec- the question of microcelebrity influence on politics remains. ondary structure was observed in both Jto and Wil. Misfolded In a two by two experiment, this study starts with a litera- conformations, obtained from the MD simulations, were used ture review on credibility, traditional celebrity, their political to guide the design of alpha-sheet , which have been influence on audiences, followed by an introduction to mi- used previously to inhibit amyloid formation in diverse sys- crocelebrities and their influence, with a method section that tems. The designed peptides were evaluated computationally leads to a few hypotheses. First, according to past literature, by docking them against misfolded conformations of Wil, and it is hypothesized that traditional celebrities are evaluated as the best performing peptide was chosen for future experimen- more credible than microcelebrities. Second, male celebri-

Undergraduate Research Program 1 www.uw.edu/undergradresearch tal work to explore its potential to limit aggregation. SESSION 1G SESSION 1G TOWARDS BETTER UNDERSTANDING TOWARDS BETTER UNDERSTANDING OF HUMAN DISEASESTHROUGH OF HUMAN DISEASESTHROUGH MOLECULAR BIOCHEMISTRY Session Moderator: Valerie Daggett, Bioengineering MOLECULAR BIOCHEMISTRY MGH 238 Session Moderator: Valerie Daggett, Bioengineering 12:30 PM to 2:15 PM MGH 238 * Note: Titles in order of presentation. 12:30 PM to 2:15 PM * Note: Titles in order of presentation. Alpha-Sheet Peptides Inhibit Functional Amyloid Formation of Streptococcus mutans Biofilms Adhered to Toward a Peptide-Based Therapeutic for Type 2 Diabetes Artificial Salivary Pellicles Steven Hsu, Senior, Bioen: Nanoscience & Molecular Engr Natasha Anay Paranjapye, Senior, Bioengineering Mary Gates Scholar Mary Gates Scholar Mentor: Valerie Daggett, Bioengineering Mentor: Valerie Daggett, Bioengineering

Type 2 diabetes (T2D) is a disease associated with pancreatic Streptococcus mutans is an acidogenic bacterial species that islet β-cell failure; especially, the loss of β-cell mass. Ap- predominates in the oral microbiome. S. mutans binds to the proximately 75% of patients who start with one medication salivary pellicle, a layer of that forms on the tooth will need multiple to control the progression of this disease. surface and forms acids after metabolizing sugars. Accumu- With no cure and numerous secondary complications - blind- lation of S. mutans biofilms leads to cavity formation, and ness, kidney failure, heart attack, and stroke - T2D places an when the bacteria travels to and infects the heart, can lead enormous burden on our society and healthcare system today; to infectious endocarditis. Therefore, decreasing accumula- The disease is projected to be the seventh leading cause of tion of S. mutans is a key concern. Recent evidence suggests death by 2030. Islet amyloid polypeptide (IAPP) deposition that S. mutans is among the bacterial species that utilize func- is observed in approximately 90% of T2D patients. While hu- tional amyloid fibrils in its biofilms. are insoluble man IAPP (hIAPP) is amyloidogenic, forming amyloid fibrils fibrillar aggregates with a cross-ßstructure, and func- and deposits, IAPP from rodents is not. Our group’s pre- tional amyloids are used by bacteria to provide structure and vious findings suggest that T2D and other amyloid diseases strength to their biofilms. While functional amyloid systems form soluble toxic oligomers through a non-standard α-sheet in bacteria such as E. coli and S. aureus have been investi- secondary structure. We propose a peptide-based therapeu- gated, very little is known about the mechanism or purpose of tic to combat T2D via utilizing synthetic α-sheet compounds S. mutans functional amyloids. Polyphenolic small molecule complementary to the amyloid-associated α-sheet structure to epigallocatechin gallate, or EGCG, is an amyloid inhibitor target the toxic oligomer form of hIAPP. In this study, we ad- in S. mutans biofilms. Previous results from our lab suggest dressed the efficacy of this peptide-based therapeutic through that amyloid fibrillization progresses via an intermediate that inhibiting the aggregation of hIAPP via a Thioflavin-T as- adopts a unique secondary structure, an alpha-sheet. Alter- say and neutralizing the hIAPP oligomer cytotoxicity via a nating L- and D- peptides adopt an alpha-sheet MTT cell viability assay in a human-derived pancreatic cell secondary structure and have been shown to inhibit amyloid line. The preliminary results suggest that our peptides are formation in multiple mammalian systems by binding to sol- effective in reducing hIAPP aggregation and oligomer cyto- uble alpha-sheet-containing oligomeric species. Inhibition toxicity. Moving to a more biologically relevant model, we of amyloid formation by alpha-sheet peptides suggests pres- evaluated the effects of our compounds on reducing amyloid ence of an alpha-sheet intermediate species on the pathway formation in the islet of Langerhans from transgenic mice; to functional amyloid formation. To investigate the mech- the preliminary results are encouraging. The α-sheet plat- anism of functional amyloid formation in S. mutans, alpha- form provides a novel potential therapeutic for treating T2D sheet peptide inhibitors were compared to EGCG for their and other amyloid diseases. ability to inhibit fibril formation of S. mutans adhered to an artificial salivary pellicle.

2 Development and Testing of WRANGLER for Design SESSION 1G and Modeling of Peptides and Proteins with Interactive Visual Analytics Jennifer Ann (Jenny) Ferina, Senior, Bioengineering TOWARDS BETTER UNDERSTANDING UW Honors Program OF HUMAN DISEASESTHROUGH Mentor: Valerie Daggett, Bioengineering Mentor: Matthew Childers, Bioengineering MOLECULAR BIOCHEMISTRY Session Moderator: Valerie Daggett, Bioengineering Computational simulations of protein dynamics provide an MGH 238 efficient way of predicting protein behavior and are increas- 12:30 PM to 2:15 PM ingly being applied to peptide and protein design. However, * Note: Titles in order of presentation. design tools and software focus on static structures. Incor- poration of dynamics directly or through design libraries de- Inhibition of a Synthetic Amyloid’s Aggregation and rived from dynamics simulations allows the user to focus on Toxicity by Multiple Native Amyloid Species optimization of the native dynamics of the protein for a spe- Timothy Mark Bi, Senior, Bioengineering cific purpose. Critical libraries for design, such as side chain Washington Research Foundation Fellow rotamer libraries and amino acid propensities are typically de- Mentor: Valerie Daggett, Bioengineering rived from static structures, which do not reflect behavior in dynamic conditions. Therefore, including rotamers and con- Alzheimer’s disease affects millions of individuals world- formational propensities derived from behavior during pro- wide, yet there is an astounding lack of marketed treatments tein simulations in molecular modeling and design software that can effectively slow the neurodegeneration associated should improve the design process and outcome, particularly with the disease. In the past few decades, evidence has for peptides. Additionally, current software does not allow emerged that small, soluble aggregates of beta-amyloid (Aβ) the user to adjust the main chain dihedral angles of the back- peptide known as oligomers are primarily responsible for tox- bone according to Ramachandran plots reflecting the unique icity in the brain, which has sparked research to develop in- free energy landscape of each residue. The WRANGLER hibitors targeting the toxic oligomers. However, the actual software was designed in order to include dynamic data to structure of Aβ oligomers remains unknown, in large part be- better model and design against and for dynamic systems. cause traditional methods used to determine A number of libraries derived from dynamics simulations of are ineffective due to the dynamic and heterogeneous nature all known protein folds have been incorporated. In addition, of these oligomers. This in has greatly hindered ther- the software is interactive with a graphical interface to easily apeutic development. Interestingly, a designed α-sheet pep- change and visualize geometries and analyze peptide/protein tide known as AP3 displays striking behavioral similarities properties. WRANGLER was evaluated based on ability to to Aβ under low pH, making it an ideal model for under- facilitate design of several amyloid peptide aggregation in- standing amyloid protein behavior. In addition, AP3 aggre- hibitors. Resulting designs were evaluated through molecular gation and toxicity are potentily inhibited by other amyloid dynamics simulations for their secondary structure retention species. The interactions between this synthetic amyloid and and physical properties. Control amyloid peptide aggrega- naturally-occurring amyloid species, including Aβ, are being tion inhibitors were included that have already been designed, explored both experimentally and via computer simulation, synthesized and tested experimentally in lab. Several pep- and the data are being used to design a de novo peptide in- tides designed in WRANGLER appear to be better than the hibitor. This inhibitor is being tested for its ability to inhibit controls by a variety of metrics. The next step is to synthe- amyloid aggregation and toxicity, as well as whether it can size these new designs and test them against the amyloid-beta specifically bind to heterogeneous populations of Aβ even at peptide associated with Alzheimer’s Disease to see if they low concentration. The successful completion of this project outperform our current compounds. wil result in significant progress towards understanding amy- loid behavior and aggregation. This may eventually lead to novel applications of the α-sheet structure in treatments and diagnostic assays for Alzheimer’s.

POSTER SESSION 4 MGH 206, Easel 176 4:00 PM to 6:00 PM

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