YSM Issue 93.2

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FOCUSNanoscience at once,” Piotrowski-Daspit explained.This method could provide researchersopportunities to better understand combinationtherapies in humans as well.Overcoming ObstaclesThe researchers faced a few challengeson their path to developing this improvedmicroscopy method. First, a majorconcern with nanoparticle researchis the possibility that the fluorescent dye(which is visualized) and the nanoparticleitself have unexpectedly separated, sothe dye is no longer indicating where thenanoparticle is. To address this, the teamordered a commercially available polymerthat is chemically linked to a fluorescentdye, and then imaged both thepolymer and a separate encapsulated dye.“The observation that they colocalizedserved as evidence that going forward, ifwe look only for the encapsulated dye, wecan be confident that it is also with thenanoparticle of interest,” Bracaglia said.Another concern was that measuring fluorescentagents might not be as accurateas measuring radiolabeled agents, so theteam carefully compared their experimentalhalf-lives with examples from literature.Not only did they confirm similarhalf-life values, but their method wasalso less complicated and more accessiblefor the average lab, which may not haveequipment for measuring radioactivity.Future ProjectsArmed with a more effective method tomeasure circulation half-lives of drugs,the Saltzman research group plans toABOUT THE AUTHORrapidly screen through their nanoparticlelibraries. “We are excited to see wherethese new nanoparticles go and how longthey stay in the blood, and to learn moreabout how changes to physical and chemicalproperties can affect drug deliverysuccess,” Bracaglia said.An upcoming challenge for these researchersinvolves what happens afternanoparticles are delivered into circulation.Because the liver functions to detoxifydrugs from the blood, nanoparticlesoften accumulate in the liver insteadof the desired target organ. The researchershope to discover ways to bypassthe liver, using “decoy” nanoparticles.“These molecules potentially may beused to pre-treat and take up residence inthe liver, such that anything that comesafterwards can remain in circulation longerand reach other organs,” Piotrowski-Daspitexplained.The main advantage of this novel protocolis that the improved quantitativefluorescent microscopy has drasticallyreduced sample blood volume. Previouslimitations from sample blood volumeoften prevented experiments involvingessential animals with rare tumors or diseases.“You normally don’t want to wastethese animals doing a half-life experiment.If you’re treating the tumor, youwant to save these animals to see if thetreatment worked,” Bracaglia said. Drugcirculation, however, might significantlydiffer between non-experimental anddiseased animals. With this new timeand-costeffective, accessible microscopymethod, scientists may soon be able toscreen a wide range of therapeutic agentsand provide more accurate measurementsfor preclinical studies, enabling researcherseverywhere to answer the growingneed for innovative drugs. ■ANNA SUNANNA SUN is a senior in Jonathan Edwards College majoring in Molecular, Cellular and DevelopmentalBiology. She currently serves as Managing Editor for the . Outside of , shestudies riboswitches, volunteers in the hospital, and reads with New Haven youth. She also enjoysdancing and exploring the food scene in New Haven with her friends.THE AUTHOR WOULD LIKE TO THANK Laura Bracaglia, Alexandra Piotrowski-Daspit, and MarkSaltzman for their time and thoughtful discussions about their research.FURTHER READINGBracaglia, L. G., Piotrowski-Daspit, A. S., Lin, C., Moscato, Z. M., Wang, W., Tietjen, G. T., & Saltzman, W.M. (2020). High-throughput quantitative microscopy-based half-life measurements of intravenouslyinjected agents. PNAS, 117(7), 3502-3508.Bracaglia, L. G., Piotrowski-Daspit, A. S., & Saltzman, W. M. (Personal interview, March 4, 2020).FDA. (2018, January 4). Step 3: Clinical research. The Drug Development Process. https://www.fda.gov/patients/drug-development-process/step-3-clinical-researchSmith, Yolanda. (2018, August 23). News Medical Life Sciences. https://www.news-medical.net/health/What-is-the-Half-Life-of-a-Drug.aspxFluorescence fundamentals. biological and biomedical research. , 14067-14090.Saltzman Research Group. (n.d.). Our research. https://saltzmanlab.yale.edu/gallery/our-researchLe, J. (2019, June). Merck Manual Consumer Version. https://www.merckmanuals.com/home/drugs/administration-and-kinetics-of-drugs/drug-administration12 Yale Scientific Magazine September 2020 www.yalescientific.org
Computational BiologyFOCUSDRIVERSPREDICTINGTHE FUTUREIMAGE COURTESY OF WIKIMEDIA COMMONSusing drivermutationsto estimatetumor growthpatternsBYMARIAFERNANDAPACHECOEver since that split second in whichyour parents’ gametes fused togenerate your life, the cells that makeup who you are have not stoppeddividing, even right now. As theyreplicate, it is likely that their DNA will mutate,incorporating new traits into the genetic codethat writes their fate—what structure they willadopt, what function they will perform, whatpurpose they will serve. While some mutationscan be responsible for traits like ginger hairor the absence of wisdom teeth, or even attimes go completely unnoticed, other far moredangerous ones hold the power to corrupt acell’s machinery, culminating in grave rippleeffects that can make all systems go haywire.www.yalescientific.orgSeptember 2020 Yale Scientific Magazine 13
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