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THE TRAINING PAGESpecial to the Training PageBroadening Your Audience Beyond Your Specialty AreaBY JENNIFER KAGANScience communication has neverbeen more impor tant than duringthe past year. Suddenly, everyone isinterested in a category of viruses thatscientists have been quietly studyingfor decades. We all want to know whenlife will return to normal, and we aresearching for answers. Unfortunately,misinformation spreads faster thanfactual information: People pay attentionto simple explanations and sometimesignore what they do not comprehend. Ifwe want people to trust the science, wehave to help them to understand it.I am a nonscientist who has taughtadvanced English classes to scientiststhrough the Foundation for AdvancedEducation in the Sciences since 2017.Many of my students are quite proficientin English, having studied the language indepth, but they want to make better useof their language skills to become moreeffective communicators. I challenge mystudents to explain the important aspectsof their work more clearly.Regardless of your native language, itis much easier to speak to people insideyour specialty area than to those outsideyour area of expertise. After all, the peoplein your field share a common language,full of specialized terms unique to youand your colleagues. But the more youpractice speaking to people outside yourspecialty, the more comfortable you willfeel. You’ll be rewarded with interestingconversations while doing your part toeducate the public about science.The first step in getting your audienceto understand what you are saying is toget them to listen. Here are some tips thatcan help when you want to engage in aconversation with someone who knowsnothing about what you do:4THE NIH CATALYST MAY–JUNE 2021Tip 1: Tell your audience what excitesyou about what you do.Do you like the excitement of discoveringsomething before anyone else? Use ananalogy to explain how much we have yetto learn about how our bodies work. You cancompare what you do to being an explorer.Make identifying a new protein sound asexciting as discovering a new planet.Tip 2: Think about your audience’sinterests and find a connection.How does your specialty area connect tosomething that the average person canunderstand? When your audience includespeople in the general public, you may needto explain words that are part of your vocabulary as a scientist, but are new to them. Forexample, describing CRISPR-Cas9 geneediting as genetic scissors can provide ahelpful visual. If you are a basic scientist,give an example of how your work is important in providing vital information that leadsto treatments and cures for diseases.Tip 3: Leave your audience wanting tohear more.Give bite-sized pieces of information in thesimplest language possible, then pause tolet your audience digest it. When your listeners get a taste of what you know andstart asking questions, you’ve succeeded incommunicating about science.Tip 4: Tell a Story.People of all ages love stories. One of mystudents likes to tell her seven-year-old sonstories in which the main characters areantibody superheroes. Wouldn’t you preferto learn about the immune system throughher stories instead of a boring PowerPointpresentation?My students have told me thatspeaking to members of the public can beboth challenging and rewarding. It’s “anexciting challenge because you can’t useall the [scientific] jargon when you talkto a general audience,” said postdoctoralfellow Omar Jose (National Instituteof Diabetes and Digestive and KidneyDiseases), who gave a short talk recentlyabout vaccines at a community learningevent called Celebrating Scientists.“Whenever I give a presentation, Itry to make the message as simple aspossible without leaving out any criticalinformation. It takes time to developthis ability, but it pays off because it’s anexcellent way to engage the audience.”Remember, if we want people totrust the science, we need to help themunderstand it. So the next time someoneasks what you do or wants to know aboutyour day, think of it as a communicationschallenge that you’re ready to takeon. And if you are asked to speak atyour child’s school for career day, say“Yes!” Think of it as a communicationschallenge, and a challenge that you’reready to take on.Jennifer Kagan, a faculty developmentspecialist with NIH’s Foundation forAdvanced Education in the Sciences (FAES)[https://faes.org], teaches courses in Englishcommunication skills and supports facultyin delivering high-quality, graduate-levelcourses to the NIH community. Before joiningFAES in April 2021, she was English Now!’sDirector of Program Development and helda joint appointment with FAES, teachingfor English Now! Outside of work, she enjoysbiking, playing Scrabble, and spending timewith her family.

THE SIG BEATNEWS FROM AND ABOUT THE SCIENTIFIC INTEREST GROUPSNew SIG: AsianAmerican PacificIslander HealthNew SIG: PrecisionOncologyCancer is a constellation of diseasestypified by the uncontrolled accumulationof cells. Given the diversity of the cell typesthat can be transformed, cancer can affectnearly every tissue and organ. Taking intoaccount the variety of genetic variations,epigenetic influences, and environmentalL. ALEXANDER/THINKSTOCK.COMThe Asian American Pacific IslanderHealth Scientific Interest Group (AAPIHSIG) is open to all in the intramuraland extramural NIH community who areinterested in research related to the healthof AAPIs. The SIG provides a forumto foster scientific communication, shareand disseminate information, facilitatecollaborations, provide education, assessresearch needs, and make recommendationsto NIH leadership that aims to stimulateresearch and improve the health and wellbeing of the AAPI population. Regularactivities include monthly (or quarterly)meetings as well as research and educationseminars (virtual or in-person). Otheractivities may include holding conferencesand lectures in collaboration with otherNIH groups and other Federal and nonFederal entities; conducting joint activitieswith the Federal Asian Pacific AmericanCouncil; and encouraging extramuralprogram staff to develop grant-fundingopportunities. The SIG co-chairs are DanXi (NCI) and Phuong-Tu Le (NIMHD).C o-adv isor s i nc lude Kelv in Choi(NIMHD) and Xinzhi Zhang (NCATS).For information, go to https://oir.nih.gov/sigs/AAPI-HSIG or contact Dan Xi(xida@mail.nih.gov).factors that drive the development oftumors, one quickly appreciates that anygiven cancer is essentially a patient-specificdisease. From this perspective, precisionin the treatment of cancer is essential inproviding the best care for patients.At the NCI-Center for Cancer Research’s(CCR’s) online PI retreat, held in March2021, clinicians, pathologists, principalinvestigators, staff scientists, and staffclinicians expressed an interest in creatinga Precision Oncology Interest Group (POIG).Short-term goals. 1) Discuss, plan,implement, and execute the current CCRinitiative to perform standardized genomicanalyses (RNA sequencing, exomesequencing, methylation analysis) on a largecohort of NCI patients; 2) Use these datato drive collaborative, predictive, prognosticbiomarker discovery, and precision-therapystrategies for improving patient outcomes.Long-term goals. 1) Discuss andimplement best sample-acquisition andmanagement practices; 2) Discuss andimplement the best technologies andinformatics to help discover candidates fortargeted therapies; 3) Rationally designclinical trials in oncology with a focus onprecise therapies that have the potential tomaximize benefit and minimize side effects.The POIG aims to foster effectivecommunication across the basic andclinical research oncology communitiesand to harness NIH’s translational powersto advance cancer precision therapies. ThisPOIG effort, initially proposed by BrigitteWidemann (NCI), will be co-chaired byNCI scientists Padma (Sheila) Rajagopal,Antonios Papanicolau-Sengos, and ArtShaffer; advisors are Eytan Ruppin andKenneth Aldape. All are welcome toparticipate and contribute suggestions fordiscussion topics and speakers (includingyourself, of course). For more information andto join the LISTSERV, go to st-group.New SIG: CancerMetabolismThe Cancer Metabolism InterestGroup aims to provide a forum forindividuals from NIH and the extramuralcommunity to discuss basic, translational,and clinical research related to metabolismand the intersection of metabolismwith immunology. The wide scope ofseminar topics will reflect the increasingrecognition that the study of subcellular,cellular, and whole-body metabolismis relevant for understanding metabolicheterogeneity, drug resistance, dietsin cancer, cancer biology, and tumorprogression. The group will meet thefirst Monday of each month (virtuallyfor now). Each meeting will featureone 60-minute presentation from anintramural or extramural senior scientistor two 30-minute presentations fromtrainees. Senior advisers are Mark Gilbert(NCI-CCR) and Dan McVicar (NCICCR). The SIG chair is Mioara Larion(NCI-CCR). For more information, go st-group or contact Mioara Larion(mioara.larion@nih.gov).For a full list of NIH scientific interest groups,go to yst5

FEATUREPhage TherapyCONTINUED FROM PAGE 1Series (WALS) on March 10 and March17 respectively.Evolutionary trade-offsTurner is the Rachel Carson Professor ofEcology and Evolutionary Biology at Yaleand a prominent expert on evolutionarytrade-offs (he earned his Ph.D. withRichard Lenski, famous for his ongoing33-year-old long-term evolution experimenton bacteria). A trade-off occurs when naturalselection improves one trait at the expenseof another. Turner shared his findings thatdemonstrated how evolutionary trade-offsbetween AR and phage resistance could beused in phage therapy.His research team isolated phages thatenter a bacterial host by selectively targetingthe elements used by the bacteria to developAR. The idea was simple: If the bacteriaevolve phage resistance by modifyingthese elements, it will compromise theirantibiotic resistance, making the bacteriasusceptible to antibiotics once again. Asynergistic treatment using phages togetherwith antibiotics would leave little chance forthe antibiotic-resistant bacteria to escape.Bacteria often develop AR by expellingdrugs through proteins known as effluxpumps. Turner showed how a phage thatbinds to an efflux pump of Escherichia coli(E. coli) results in the selection of phageresistant bacteria that are now sensitive totetracycline. A similar approach could targetvirulence factors. For example, his teamfound a phage that invades Pseudomonasaeruginosa by attaching to pili, hair-likeappendages on the surface of bacteria toCREDIT: MANOJ RAJAURE, NCIThe exciting news is that phage therapyis making a comeback; recent case studieshave been successful in using phages as anexperimental therapy.The therapy still has a long way to goas it is not yet generally approved by theFDA. And, as with antibiotics, bacteria alsodevelop phage resistance. The evolutionaryarms race between phages and bacteria hasbeen going on for billions of years—whichis critical to understand for phage therapyto become a success. Two experts, PaulTurner from Yale School of Medicine (NewHaven, Connecticut) and Michael Laubfrom MIT (Cambridge, Massachusetts),shared their research on the evolutionaryinteraction between phages and bacteria andits significance to phage therapy at the NIHDirector’s Wednesday Afternoon LectureTransmission electron micrograph of a bacteriophage isolated from sewage. The phage kills a pathogenic strain of E. coli isolated from a patient with a urinary tract infection.6THE NIH CATALYST MAY–JUNE 2021

FEATUREhelp in movement and surface adherenceduring infection. When the bacteriumdeveloped phage-resistance by losing thepili, it became avirulent (more vulnerableto the immune system) due to its inabilityto form biofilms and to move around.“But there is a cautionary tale, and youshould know what you are doing beforeusing phages for therapy,” Turner said.Sometimes, instead of causing a trade-off,mutations cause a trade-up; they conferresistance to both antibiotics and phages.The last part of Turner’s talk focusedon emergency phage therapy. His team wasgranted FDA approval to treat a patientwho developed a chronic AR infection afterundergoing an aortic arch replacement. Theychose a phage that used an efflux pumpfor entering the bacteria and predicted thatthe phage would kill the existing microbepopulation while exerting selection pressureon the bacteria to develop phage resistance,compromising their ability to maintain AR.Consistent with the evolutionary trade-offtheory, a single application of the phageand a previously ineffective antibiotic(ceftazidime) resolved the infection withno sign of recurrence.In another case, a 22 year-old patientwith cystic fibrosis undergoing pulmonaryfailure had a high concentration of ARbacteria in her sputum. After a phagetherapy treatment given via nebulizer,her lung function improved significantly.Interestingly, the treatment resulted in apopulation of bacteria that became sensitiveto almost all antibiotics, opening the doorto previously unavailable treatment options.Turner is hopeful that phage therapywill be used in clinics soon. To date, YaleNew Haven Hospital has successfullytreated over 13 patients with AR infectionsusing the emergency therapy. And thingsare moving in the right direction; Thehospital was recently granted FDA approvalto begin phage-therapy clinical trials.From proteins to phagesLaub is a professor of biolog y atMassachusetts Institute of Technologyand a Howard Hughes Medical InstituteInvestigator. He studies the coevolutionof proteins and the selective pressuresthat drive the evolution of bacterialsignaling pathways (mechanisms thatallow bacteria to process information andrespond to environmental changes). But“the coevolution of proteins is dear to myheart”, he said.Laub’s ongoing work on the coevolutionof toxin-antitoxin (TA) protein pairs(referred to as TA systems in bacteria) ledto his foray into the world of phages. ATA system consists of a toxin gene and anassociated antitoxin. The toxin is always aprotein, and the antitoxin can be either aprotein or a noncoding RNA. These systemsare widespread in the bacterial kingdom, butwhy bacteria carry them remains a mystery.Laub's team discovered that cloning theTA systems found in several E. coli strainsinto E. coli K12 (a widely used laboratorystrain of the bacterium) resulted in phageresistance.Interestingly, the bacteria did notdevelop broad phage resistance, suggestingthat TA systems seem to provide tailoredprotection only against specific phages. Forexample, one of the TA systems preventsthe production of new viral particles bydestroying the phage RNA. These findingsestablish TA systems in bacteria as anotherarm of immunity against phages in theongoing evolutionary arms race.“Phages fight back,” Laub said. Histeam identified a phage variant that evolveda counter-defense against one of the TAsystems. This phage amplified a region ofits DNA that encoded a protein capable ofneutralizing the toxin, allowing the phageto propagate.Both Laub and Turner are exploringconcepts with far-reaching implicationsin phage therapy. Turner also believesthat his work may help answer some biggerquestions, such as how do we predict theemergence of viruses in new hosts? Theinvestigation into evolutionary trade-offsbetween phages and bacteria might justreveal some clues.Subhash Verma is research fellow in NCI’sLaboratory of Molecular Biology. In his sparetime, he enjoys exploring nature, playingcricket and volleyball, and biking.PAUL TURNERTo view a videocast of Turner’s WALS lecture“Phage Therapy to Combat Infections byAntibiotic-Resistant Bacteria,” delivered onMarch 10, 2021, go to: https://videocast.nih.gov/watch 41443.MICHAEL LAUBTo view a videocast of Laub’s WALS lecture,”Innate Immunity for Bacteria Against Phage,”delivered on March 17, go to https://videocast.nih.gov/watch 41451 (HHS only).https://irp.nih.gov/catalyst7

CATALYTIC RESEARCHIntramural Research BriefsCREDIT: NINDSNINDS, NCI, NIAMS, NICHD, NEI: DNAThe NIAD team had previously establishedDAMAGE “HOT SPOTS” DISCOVERED WITHINa human cerebral organoid system—a smallNEURONScluster of human brain cells grown in a lab fromResearchers at NIH and the University of Sussexskin cells. The cerebral organoids have been(Falmer, England) have identified “hotspots,”shown to accurately predict neurotoxicity—in neuron genomes that appear to accumulateand therapeutic benefits—of drug treatmentsDNA damage known as single-strand breaksin humans.(SSBs)—a finding that has the potential toThe researchers infected the cerebralreshape the way we think about DNA damageorganoids with pathogenic prions and thenand its role in neurobiology.tested pentosan polysulfate (an establishedThe scientists found that the mostantiprion compound), which successfullyprominent concentrations of SSBs localized todelayed prion propagation when applieddistinct regions of DNA called enhancers, whichboth prophylactically and after an establishedcontrol nearby gene activity. One way a cellinfection. The findings demonstrate the utilitycan influence gene expression is by applyingof cerebral organoids as a model for screeningNCI: ENGINEERED IMMUNE CELLS MAYa chemical tag known as a methyl group totherapeutic drug candidates to treat humanPREVENT CANCER SPREADspecific sites on its DNA; SSBs accumulatedprion diseases.(NIH authors: B.R. Groveman,Scientists at NCI have developed a form ofwhen the methyl group had been removed.N.C. Ferreira, S.T. Foliaki, R.O. Walters, C.W.NINDS: “Hotspots” in neuron genomes that appear to accumulate DNA damage. Neurons (labeled in purple) showsigns of an active DNA repair process (labeled in yellow).The cells’ DNA itself is labeled in cyan (in this image, overlap between cyan and yellow appears green).immunotherapy that prevents and slowsThe researchers proposed that the absentWinkler, B. Race, A.G. Hughson, and C.L. Haigh,cancer metastasis in mice. They studied micemethyl group resulted in the formation ofSci Rep 11:Article number 5165, 2021)implanted with rhabdomyosarcoma, a typeSSBs. And, at least in neurons, the failure to[BY NATALIE HAGEN, NCATS]of cancer that develops in the muscles andproperly repair DNA damage, not the damagespontaneously metastasizes to the lungs. Theitself, could dysregulate gene expression,team first examined immune cell changes in thethereby contributing to the development oflungs before metastasis but after muscle-tumorneurodegenerative diseases. (NIH authors: W.development. They found that several immuneWu, S.E. Hill, W.J. Nathan, J. Paiano, E. Callen,cell types—in particular myeloid cells—wereD. Wang, K. Shinoda, N. van Wietmarschen,attracted to the premetastatic site. However,J.M. Colón-Mercado, D. Zong, R. De Pace,instead of sending signals to recruit cancer-H. Shih, S. Coon, M. Parsadanian, R. Pavani,fighting immune cells, the myeloid cells wereS. Park, S.K. Jung, C. Chen, R. Casellas, M.E.actively suppressing the immune response.Ward, and A. Nussenzweig, Nature 2021;The researchers created red myeloid cells (GEMys) that produce[BY CHARLESICE GRABLE-HAWKINS, OD]interleukin 12 (IL-12). The mice treated withGEMys had decreased metastatic cancerand muscle-tumor size and lived longer thancontrol mice. GEMys in combination with othertreatments even prevented cancer recurrence.The team plans to tes

CREDIT: NASA/JPL-CALTECH This illustration depicts NASA's Perseverance rover operating on the surface of Mars. Perseverance, which landed at the Red Planet's Jezero Crater on February 18, 2021, will search for signs of life and test technologies that may help determine whether humans could one day inhabit the planet. CONTINUED ON PAGE 12