Chasing cancer ALSO INSIDE THIS ISSUE: Real science gets inked! with dogs What your mentor wants you to know

CONTENTS

NEWS FEATURES PERSPECTIVES

2 10 46 PRESIDENT’S MESSAGE CHASING CANCER WITH DOGS CAREER INSIGHTS Review the reviewers The courage to find myself 14 4 MEET BERNHARD KÜSTER 48 NEWS FROM THE HILL EDUCATION Is the Precision Medicine Initiative 48 Six things your mentor wants really necessary? 16 STEAM you to know (but probably won’t think to tell you) Real science gets inked! 5 50 Action plans and best practices MEMBER UPDATE 20 for undergraduate education 6 ANNUAL MEETING SPECIAL SECTION 52 NEWS 22 Theme Articles OUTREACH 6 Down Syndrome strides 34 Meet the 2016 plenary lecturers Drinks, chips and STEM 7 Technique of the month 8 20 JOURNAL NEWS 8 Discovering novel drugs to target G-protein–coupled receptors 9 More good news about aspirin’s effects on cardiovascular disease 8

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10 Comparative oncologists are looking to dogs for clues about human cancers. Chasing cancer ALSO INSIDE THIS ISSUE: Real science gets inked! with dogs What your mentor wants you to know

OCTOBER 2015 ASBMB TODAY 1 PRESIDENT’S MESSAGE

THE MEMBER MAGAZINE OF THE AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY Review the

OFFICERS COUNCIL MEMBERS Steven McKnight Squire J. Booker reviewers President Karen G. Fleming Gregory Gatto Jr. Natalie Ahn Rachel Green By Steven McKnight President-Elect Susan Marqusee Karen Allen Jared Rutter Secretary Brenda Schulman large fraction of the National new appointments to the HHMI. Michael Summers Institutes of Health’s budget is The HHMI leaders continually judge Toni Antalis spent in support of extramural the capabilities of their contracted Treasurer ASBMB TODAY EDITORIAL A ADVISORY BOARD research. These funds are the lifeblood reviewers too. “We monitor reviewer EX-OFFICIO MEMBERS Charles Brenner of biomedical research in the United performance on an ongoing basis. If a Squire Booker Chair States. NIH grant applications are reviewer exhibits anything other than Wei Yang Michael Bradley Co-chairs, 2016 Annual Floyd “Ski” Chilton reviewed, in most instances, by mem- substantial competence, that person is Meeting Program Cristy Gelling bers of 176 study sections organized relieved of his orher responsibilities,” Committee Peter J. Kennelly by the Center for Scientific Review. Tjian told me. Peter J. Kennelly Rajini Rao How can we know whether these The NIH is composed of 27 insti- Chair, Education and Yolanda Sanchez Professional Development Shiladitya Sengupta reviewers are doing a good job? Are tutes, each headed by a director. On Committee Carol Shoulders the reviewers reviewed? average, these 27 institutes disburse Daniel Raben The review of reviewers happens in around $500 million each in external ASBMB TODAY Chair, Meetings Committee spades at the Howard Hughes Medical funding per year. This is about half the Angela Hopp Takita Felder Sumter Executive Editor, Institute. The senior leadership of amount of funding disbursed annually Chair, Minority Affairs [email protected] Committee the HHMI, including its president, by the HHMI. If the HHMI can Lauren Dockett Robert Tjian, sits in on each and review its reviewers effectively in the Thomas Baldwin Managing Editor, Chair, Outreach Committee [email protected] every investigator review. They also disbursement of $1 billion annually, Wes Sundquist Rajendrani Mukhopadhyay listen to the talks of candidates for it should be possible for individual Chair, Public Affairs Chief Science Correspondent, Advisory Committee [email protected] Blake Hill Valery Masterson Chair, Publications Designer, Committee [email protected] Lauri Pantos F. Peter Guengerich Manager of Publications Interim editor-in-chief, JBC Technology, [email protected] Herbert Tabor Ciarán Finn Co-editor, JBC Web Publication Assistant, [email protected] A. L. Burlingame Editor, MCP Allison Frick Media Specialist, Edward A. Dennis [email protected] Joseph L. Witztum Barbara Gordon Co-editors, JLR Executive Director, [email protected]

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www.asbmb.org/asbmbtoday PRINT ISSN 2372-0409 Articles published in ASBMB Today reflect solely the authors’ views and not the official positions of the American Society for Biochemistry and Molecular Biology or the institutions with which the authors are affiliated. Mentions of products or services are not endorsements.

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2 ASBMB TODAY OCTOBER 2015 institutes of the NIH to do the same. about the operation of roughly six or less than outstanding performance by Each institute director should care seven study sections. The director of a study section reviewer, much less as passionately about the disburse- the National Cancer Institute should the person chairing a study section, ment of his or her institute’s funds care about the five to 10 study sections they would be expected to relieve that as the president of the HHMI cares that review research proposals in the person and replace him or her with a about the distribution of his institute’s field of oncology; the director of the competent one. own funds. Like the president of the National Institute of Mental Health For all I know, there might be fed- HHMI, the NIH institute directors should care about the handful of study eral rules in place that directly prevent should keep a finger on the pulse of sections that review proposals relating this. If so, how incredibly foolish it the review process controlling dis- to neuroscience; and on and on. would be to prevent NIH institute bursement of their precious funds. As If each study section meets three directors from directly monitoring and such, I offer that it is only reasonable times a year, and if each institute guiding the spending of their substan- to ask that NIH institute directors were paired with the handful of study tive budgets. pay as much attention to the research sections covering the research most Recognizing that these ideas likely review process as does the president relevant to its mission, each institute will be deemed ridiculous and impos- of the HHMI. NIH institute direc- director and his or her leadership team sible to implement, I close by asking a tors and their senior staff should be would need to sit in on roughly 20 simple question: Were we just starting at study section meetings just as the study section meetings per year. A bit to devise a system to disburse federal president of the HHMI and its senior less than every other week, institute grant dollars in support of biomedical leadership are at each investigator directors would spend two days ensur- research, would we choose the hands- review. ing the quality of the study section on methods of the HHMI or the How might it be possible for the and its decisions about funding. This hands-off methods of the NIH? NIH to review its reviewers? Let’s con- would consume about a quarter of the sider what would be expected of NIH time of each institute director. institute directors were they to pay If institute directors and their lead- Steven McKnight (steven. [email protected]) keen attention to how their funds are ership staffers were embedded deeply is president of the American distributed to extramural researchers. in the review process, they could Society for Biochemistry and Knowing that there are 176 study sec- monitor the performance of review- Molecular Biology and chairman tions and 27 institutes, each institute ers directly. If institute directors and of the biochemistry department at the University director would — on average — care their leadership staff noted anything of Texas-Southwestern Medical Center at Dallas.

OCTOBER 2015 ASBMB TODAY 3 NEWS FROM THE HILL Is the Precision Medicine Innitiative really necessary? By ASBMB Policy Staff

resident Obama introduced the $200 million in their appropriations sets advances the field of big data. Precision Medicine Initiative bills. Under the austerity of the Bud- While the NIH grapples with P during his 2015 State of the get Control Act, these funds will need barriers, Alphabet’s Life Sciences (for- Union address. The goals of the initia- to be taken from other programs. This merly a part of Google X) has waltzed tive are to harness not only the power could jeopardize critical research in casually into the conversation and of advanced genomic sequencing but other important fields. announced its intention to explore also of a million-patient cohort and Is it really necessary to have the the promise of precision medicine. In to develop new methods for manag- PMI to advance methods for manag- addition to developing a glucose-sens- ing and analyzing large data sets that ing and analyzing large data? ing contact lens for diabetic patients, could accelerate biomedical discovery. Independent investigators can the Life Sciences team has been National Institutes of Health propose and pursue big-data research working with scientists from Duke Director Francis Collins wrote in the questions through existing funding University and Stanford University to New England Journal of Medicine mechanisms. For example, Wladek design the Baseline Study, which will in February, “What is needed now is Minor at the University of Virginia collect anonymous genetic informa- a broad research program to encour- received an NIH Big Data to Knowl- tion from 10,000 people to create age creative approaches to precision edge grant to develop a management a baseline picture of what a healthy medicine, test them rigorously and strategy for archiving X-ray diffraction human looks like on a molecular level. ultimately use them to build the raw data and an online portal to gain The study is unlikely to face many of evidence base needed to guide clinical access to it. Minor was concerned the challenges of the PMI. If par- practice” (1). about the massive amount of raw data ticipants buy in, Life Sciences could But launching such an ambitious in his field that goes unpublished. provide both the medical and tech- initiative will not be straightforward. “What we propose is to build the nological advances of processing and Critics of the initiative point to system to keep all diffraction data utilizing genomic data from a large several barriers. First are strict privacy (and) structural data. People are say- patient cohort, and the Baseline Study rules guarding health information. ing to do that would cost millions of could deliver the type of technologi- To conduct the large-scale genomic dollars in equipment. And our request cal advances sought by the Precision studies to achieve the initiative’s goals, for equipment was $20,000. Why? Medicine Initiative without additional information about patients and their Because we use the newest technol- federal investment. genomic data must be encrypted and ogy, and we are building computers The NIH’s Big Data to Knowledge anonymized. A second obstacle is lack by ourselves quite often. Not because program already is delivering advances of communication between scientists it’s cheaper, but because we can create in data management. Life Science’s and hospitals. Robust mechanisms something (that) is better than what Baseline Study appears poised to for scientists to share big data with you can buy” (2). leverage advanced genome sequenc- doctors do not exist, and there remain Creating a resource for preserving ing to enhance our understanding of major barriers to sharing electronic this raw data will allow other scientists health. Bogged down in privacy laws patient health records among doctors. to gain insight from experiments that and funding battles, the PMI may not Finally, finding a million volunteers otherwise might have gone unpub- even be necessary. willing to relinquish their genetic lished, and developing a management Send questions or comments information could be challenging. strategy for wrangling massive data to [email protected]. Obama’s fiscal 2016 budget sought $215 million for the initiative. In REFERENCES response, the U.S. House of Represen- 1. http://www.nejm.org/doi/full/10.1056/NEJMp1500523 tatives and the U.S. Senate proposed 2. http://bit.ly/1KPHZN7

4 ASBMB TODAY OCTOBER 2015 MEMBER UPDATE

Hudson receives Marletta wins to complications from Parkinson’s disease. He was 92. Born on Nov. Earl Sutherland Prize Alfred Bader Award 12, 1922, in Portland, Ore., Labbé’s Billy G. Hudson, The American interest in chemistry started in high the Elliott V. New- Chemical Society school. After a short stint in the navy, man professor of honored Michael A. he finished his undergraduate degree medicine and profes- Marletta with the at the University of Portland and sor of biochemistry, 2015 Alfred Bader later obtained a Ph.D. in biochem- HUDSON pathology, microbiol- MARLETTA Award in Bioinor- istry from Oregon State University. ogy and immunology, and cell and ganic or Bioorganic Chemistry. The In 1958, Labbé joined the medical developmental biology at Vanderbilt award, which comes with a $5,000 faculty at the University of Washing- University, won the Earl Sutherland prize, is sponsored by the Alfred R. ton, where he worked his entire career. Prize for Achievement in Research Bader Fund and recognizes a scien- Beginning in the department of pedi- in August. Vanderbilt established the tist’s outstanding achievements at the atrics, Labbé joined the department prize in 1976 and presents it annually intersection of biology and organic or of laboratory medicine in 1974 and to a faculty member who has garnered inorganic chemistry. Marletta holds became the head of clinical chemistry critical reception and recognition the CH and Annie Li chair in the in 1980. Labbé’s research interests nationally and internationally for molecular biology of diseases at the included the study of porphyrins, achievements in research, scholarship University of California, Berkeley, metalloporphyrins and other pyr- or creative expression. The prize comes where he is a professor in the depart- role compounds, and he developed a with an engraved pewter cup and a ments of chemistry and molecular section for the school on nutrition. A purse of $5,000. Hudson’s research and cell biology. He long has explored conservationist who enjoyed interna- focuses on the structure and function nitric oxide signaling and uncovered tional travel, photography and music, of type IV collagen. He has discovered many aspects of nitric oxide function. Labbé married Norma Lee Wiley in and characterized collagen-IV proteins More recently, his lab also has under- 1955. Norma Lee was a registered in which structural alterations cause taken investigations of polysaccharide nurse who shared Labbe’s interest in the pathophysiology of four kidney monooxygenases. the role research played in the medical diseases. He also discovered the novel field. In her honor, Labbé founded sulphur-nitrogen bond that stabilizes IN MEMORIAM: the Robert F. and Norma Lee Labbé collagen-IV networks. Additionally, Endowed Faculty Fellowship in Labo- Hudson co-founded the Aspirnaut Robert Labbé ratory Medicine at the University of program, which helps develop and Robert Fer- Washington. The fellowship supports promote science, technology engineer- dinand Labbé, the laboratory research programs of ing and math education for rural and professor emeritus faculty members who are early in their underrepresented K – 20 students at the University of careers. through internships and the beaming Washington, passed LABBÉ of STEM labs into classrooms. away in March due Written by Erik Chaulk

Scholarship update and the Minority Affairs Com- in the summer he volunteers as an mittee is pleased to announce it EMT for underprivileged commu- After our Septem- has awarded Nicolas Oropeza of nities in Sonora, Mexico. Oro- ber article on the Arizona State University one of the peza is passionate about sharing his American Society five scholarships. background and experiences with for Biochemistry Oropeza is studying biological those from diverse groups and says and Molecular sciences at the Arizona State Univer- he wants to demonstrate that “their OROPEZA Biology’s Distin- sity School of Life Sciences, where barriers are not limitations on what guished Undergraduate Scholar- ship was published, a change in he also volunteers as a mentor to they can accomplish.” He intends to recipients was announced. Shelby incoming freshmen. He is a trained graduate from ASU and then enter Newsad declined her scholarship, emergency medical technician, and a joint Ph.D./M.D. program.

OCTOBER 2015 ASBMB TODAY 5 NEWS Down syndrome strides By Indumathi Sridharan

amed after John Langdon restoring neuronal cells. Down, an English physician Other researchers are investigating N who first described the disorder the biochemical mechanisms behind in 1866, Down syndrome is the most cognitive defects observed in people common cause of birth defects in with Down syndrome. Huaxi Xu and the U.S. Every year, 6,000 babies are colleagues at the Sanford–Burnham born with the congenital disorder, and Medical Research Institute found that the Centers for Disease Control and a protein called sorting nexin 27, or Prevention reports that cases of Down SNX27, is abnormally low in people syndrome have increased by 24 per- with Down syndrome. SNX27 helps cent in recent years. Although there neurons retain glutamate recep- is no standard treatment, children tors, which is essential for synaptic IMAGE COURTESY OF UPO649 1112 MREYCOR1, A with Down syndrome can develop WIKIMEDIA COMMONS USER signaling and brain function. Xu’s basic physical, cognitive, language and A third copy of chromosome 21 in each cell causes team showed that those with Down social skills with specialized education Down Syndrome. syndrome have low levels of SNX27 and care. During October’s National because the extra chromosome low muscle tone, short stature and Down Syndrome month, the National overproduces microRNA-155, a key an upward slant to the eyes. Down Down Syndrome Society advocates inhibitor of SNX27 (3). syndrome also causes heart defects, the importance of early intervention In 2013, the National Institutes of cognitive impairment, language delays and celebrates the unique strengths Health launched a national registry and poor memory. and talents of those with the for Down syndrome called DS- syndrome. Connect. This centralized website What are the latest enables easy exchange of information What causes Down research developments? between patients, doctors and scien- tists. In 2015, the NIH introduced a Jeanne Lawrence and colleagues syndrome? Web portal within DS-Connect that at the University of Massachusetts Down syndrome occurs when allows approved scientists to access Medical School are exploring chro- chromosome 21 fails to separate anonymized data about patients’ mosomal therapy for treating Down equally between two daughter cells health. The portal will help scientists syndrome. The team inserted a gene during the formation of an egg or to coordinate clinical studies with called X-inactive specific transcript, sperm. The error is called nondisjunc- eligible participants, perform cus- or XIST, into stem cells derived from tion. If the abnormal cell contrib- tomized searches and generate new trisomy 21 patients (2). XIST con- utes to a fertilized egg, the resulting research ideas based on the collective denses and inactivates one of the two embryo will have three copies of information available in the portal. X chromosomes during mammalian chromosome 21 in every cell. For this female development. When inserted reason, the syndrome is also known Indumathi Sridharan (sridharan. into the cells, XIST silenced most of as trisomy 21. The extra chromosome [email protected]) earned the genes in the extra chromosome her bachelor’s degree in bioin- disrupts transcriptional regulation 21. The silencing also improved the formatics in India. She holds a in cells via widespread changes in Ph.D. in molecular biochemistry stem cells’ ability to differentiate into chromatin structure and methylation from Illinois Institute of Technology, Chicago. She neurons. Chromosomal silencing patterns (1). did her postdoctoral work in bionanotechnology at could improve cognitive function by Northwestern University. What are the traits of the REFERENCES syndrome? 1. Letourneau, A. et al, Nature 17, 345–50 (2014). Common physical traits include 2. Jiang, J. et al, Nature 500, 296–300 (2013). 3. Wang, X. et al, Nature Medicine 19, 473–480 (2013).

6 ASBMB TODAY OCTOBER 2015 NEWS ChIP-ing away at DNA–protein interactions By Aditi S. Iyengar

What is it? ogy successfully replaced ultraviolet light with formaldehyde. Formal- The chromatin immunopre- dehyde is a global crosslinker that cipitation assay, popularly known conjugates DNA to all associated as ChIP, is a technique used to peptides, including elements of capture and examine interactions protein complexes that that do not between DNA and proteins. The interact directly with genes. The basic principle behind ChIP is the reagent increased the versatility of achievement of a selective enrich- ChIP assays and is still used as a ment of genomic material when crosslinker in many experiments. antibodies bind to and pull out protein–DNA complexes in vivo. What are its applications?

How does it work? IMAGE COURTESY OF RICHARD WHEELER, A WIKIMEDIA COMMONS USER Data from ChIP analyses aug- The assay begins with captur- ChIP captures interactions between DNA and proteins. ment our understanding of the ing a snapshot of protein-DNA mechanisms behind transcriptional interactions by fixing live cells with instead use enzymes to cut up the and epigenetic gene regulation and a crosslinking agent, such as form- native chromatin into intact DNA– spatiotemporal expression of regula- aldehyde. Once the interactions are histone complexes for further tory elements in cells, tissues and preserved or frozen within the cell, purification and analysis. sometimes organisms. Researchers chromatin is extracted and broken often combine ChIP assays with DNA down either by physical agitation or How did it come about? microarray assays, called ChIP-on- chip, to investigate the DNA targets by enzymatic fragmentation. These In the early 1980s, when research- of specific proteins, such as transcrip- chromatin fragments are subjected to ers avidly were pursuing DNA recom- tion factors or regulatory elements, on immunoprecipitation where specific bination and gene-mapping projects, a genomewide scale. A dynamic and antibodies recognize and selectively a student working with John Lis of cost-effective version of ChIP-on-chip precipitate target proteins. Any DNA Cornell University set out to explore is the ChIP-seq. It involves high- sequences attached to the proteins of an overlooked aspect of genetics: throughput sequencing of multiple interest are co-immunoprecipitated as protein–DNA interactions in vivo. DNA fragments to map precisely part of the chromatin–DNA cross- The student, David Gilmour, along global genomic binding sites of linked complex. Finally, the cross- with members of the Lis laboratory, proteins of interest. ChIP-seq, which linking process is reversed to allow became the first to use ultraviolet light boasts high signal-to-noise ratios and for further analysis. The separated to crosslink covalently proteins and robust outputs, has widened the field DNA can be identified and quantified DNA in bacterial cells. However, one of comparative genome analyses and further using standard PCR amplifica- of the limitations of using ultraviolet is a valuable approach for studying tion, cloning and sequencing. light is that it covalently links DNA disease processes and cellular function. Some protocols call for the pres- with only proteins that are in direct ervation of the native state of the contact with nucleic acid segments. Aditi S. Iyengar earned her Ph.D. chromatin, especially when mapping In 1988, while mapping the genomic in cancer biology from Louisiana for DNA targets of proteins, such locations of histones, Alexander State University Health Sciences Center New Orleans and is cur- as histone modifiers. In such cases, Varshavsky and colleagues at the researchers avoid crosslinking and rently a postdoctoral associate at Massachusetts Institute of Technol- Cornell University.

OCTOBER 2015 ASBMB TODAY 7 JOURNAL NEWS

Discovering novel drugs to target G-protein–coupled receptors By Sapeck Agrawal

henever we experi- steric sites may help regulate ence a happy feeling, the activity of one type of W a sweet smell or a receptor but not of another. bright light, we have our The second minireview, by G-protein–coupled recep- Patrick R. Gentry, Patrick tors, or GPCRs, to thank. A Sexton and Arthur Chris- plethora of signals — odors, topoulos at the Monash hormones, neurotransmit- University in Melbourne, ters and photons — exert Australia, describes the latest their biological effect by techniques, including recent activating GPCRs. Once advances in structural biol- activated by a signal, a ogy, that are being employed GPCR engages a G protein to identify molecules, both that processes GTP to acti- exogenous and endogenous, vate downstream players in that can modulate these the biological cascade. allosteric sites. Because of their func- Crystal structures of tional importance, a host GPCRs are instrumental in of drugs target GPCRs by identifying novel allosteric Each circle, or “leaf,” in the GPCR tree corresponds to a distinct GPCR, grouped mimicking a signal or block- according to sequence similarity. sites. The third minireview, ing their signal-binding by Ali Jazayeri, Joao Dias site. Most of these drugs, the University of North Carolina at and Fiona Marshall from however, are available for only a small Chapel Hill describe the various high- Heptares Therapeutics Limited, subset of GPCRs, while the majority throughput screens they and others reveals how recent technical advances of GPCRs remain untapped. have developed to circumvent this are accelerating GPCR crystallogra- As part of a recent minireview challenge and test not one but hun- phy and how profound their implica- series published in the Journal of dreds of receptors at the same time. tions are in the discovery of novel Biological Chemistry and coordinated Facilitating this enormous task are drugs. These include steps in protein by editor Henrik Dohlman at the novel tools, such as broad-spectrum purification and engineering as well University of North Carolina at Cha- readout, sophisticated bioinformat- as the use of computational programs pel Hill, pioneering scientific experts ics analysis and high-quality chemi- that simulate docking a drug onto the in the field of GPCRs offer valuable cal libraries, many available free of crystal structure of the receptor and insights into the challenges of novel charge to the scientific community to play matchmaker between drugs and drug discovery for targeting a wider accelerate the discovery of new drug candidate binding sites. variety of GPCRs as well as some very candidates. These insightful minireviews pro- creative solutions to those challenges. The other big hurdle in GPCR- vide a quick glance into the enormous One of the challenges is the need targeted drug discovery is enhancing potential of GPCRs in drug discovery for faster and more efficient ways to the selectivity of the drug – that is, and for treating a variety of diseases screen novel drugs. There are 800 making sure that the drug regulates and conditions including mood disor- members in the human GPCR super- only the desired receptor and not any ders and cardiovascular disease. family, and the traditional screening other receptor. One solution to this method involves testing one receptor problem is identifying allosteric sites Sapeck Agrawal (sapeck. at a time, usually requiring a tailor- on these receptor — sites different [email protected]) is a from the signal-binding sites — which medical and science writer with made, radio-labeled probe or assay. a Ph.D. in molecular biology. For In the first minireview, researchers can influence the activity of the more stories, visit her blog at Bryan Roth and Wesley Kroeze at protein. Drugs that bind to these allo- sapeckagrawal.wordpress.com.

8 ASBMB TODAY OCTOBER 2015 JOURNAL NEWS

More good news about aspirin’s effects on cardiovascular disease AMPK activation in macrophages may reduce development of atherosclerosis By Nicole Parker

e see commercials lipoprotein. They also demon- every day that remind strated that macrophages that W us that we have no idea are deficient of Ampk cannot when a heart attack or stroke load off cholesterol to extracel- will occur. Then, shortly after lular acceptors, which in turn that reminder, there is a plug increases foam cell formation. for aspirin. Cardiovascular dis- These findings indicate that ease has been a leading cause of Ampk activation is important death in developed countries for controlling the removal of for years, and we know aspirin cholesterol from macrophages can improve cardiovascular and that it thereby decreases health, specifically through its foam cell formation and ability to disrupt prostaglandin progression of atherosclerosis. synthesis and reduce Most importantly, the study coagulation. shows that salicylate-based Recently, the labs led by medications like salsalate, a Gregory Steinberg at McMas- dimer of salicylate, would be ter University and Morgan great drug candidates. Fullerton at the University According to Steinberg, the of Ottawa, both in Canada, team already is testing salicy- reported a new effect of late-based drugs in preclinical aspirin. In the Journal of animal models and humans. It Lipid Research, the research- will be critical to understand ers reported that salicylate, more about the role Ampk an acetylated form of aspirin, plays in the progression of improves cholesterol levels atherosclerosis. by targeting AMP-activated Fullerton emphasized: protein kinase, or AMPK, in Ampk has a role in lipid metabolism “Ampk is a kinase with more macrophages. and that the activation of Ampk than three dozen targets. It will be Macrophages are immune cells improves cholesterol levels. How- important to identify the precise that play an important role in the ever, the mechanism and importance molecular pathway or pathways that plaque formation of atherosclerosis, of Ampk in the macrophage was are responsible for the effect that is which is the primary cause for heart unknown, so the Steinberg and Ful- caused by Ampk (activation).” New attacks and strokes. Atherosclerosis is lerton labs decided to study the role information about and a better under- the buildup of cholesterol and fats in of Ampk activation in macrophages standing of the mechanism could lead macrophages in the vasculature, which loaded with cholesterol, which are to the development of new therapies causes plaque formation on the artery known as foam cells. or modifications to existing aspirin walls. This disease often is known as To activate Ampk, they used direct regimens. a silent killer, because it shows no activators that bind to Ampk, includ- symptoms until the plaque buildup ing salicylate, a byproduct of aspirin. Nicole Parker ([email protected]) is severe enough to block blood flow Activation of Ampk with salicylate is currently completing her Ph.D. and cause critical damage that even in biochemistry and molecular increased efflux of cholesterol from biology at the Johns Hopkins can lead to death. the macrophages to extracellu- School of Public Health. Researchers already knew that lar acceptors such as high-density

OCTOBER 2015 ASBMB TODAY 9 Chasing cancer with dogs Treating canine cancers is helping researchers learn more about human forms of the disease By Soma Chowdhury

10 ASBMB TODAY OCTOBER 2015 FEATURE

hunder is a middle-aged mutt occurring at with a cheery disposition. He is a rate of one T slim, with a black coat and white in every three patches on his belly and toes. His women and owner, Jeanneen Terry from Chicago, in half of all is unsure of Thunder’s pedigree. “He men. could be a lab-border collie or lab-pit “It (was) mix. I don’t know,” she says. “He is a always the rescue dog.” interplay Three years ago, Thunder broke his between the front left leg. A year later, when the environment leg was still not getting better, his bro- and genetic PHOTO COURTESY OF UNIVERSITY OF CALIFORNIA, DAVIS SCHOOL OF VETERINARY MEDICINE ken leg was amputated, and an X-ray susceptibility A dog with cancer is positioned for radiotherapy. revealed Thunder had osteosarcoma. that led to Osteosarcoma means “bone the develop- tumor” and is the most common and ment of cancer in humans and in aggressive bone cancer in dogs. It dogs,” Kastan said during the meet- usually spreads rapidly to other organs ing’s opening remarks. through the bloodstream, especially Dogs and humans have been liv- to the lungs, and eventually becomes ing together for thousands of years. fatal. They evolved together, eating similar Unfortunately, as Terry found food, breathing the same air, and out, there aren’t any good treatment living in the same homes. Elaine options for metastatic canine osteosar- Ostrander, who works on both human coma. Furthermore, traditional canine and canine genetics at the National cancer treatment is expensive, and she Human Genome Research Institute, couldn’t afford it. But a friend of hers notes that dogs and humans also have mentioned a clinical trial program at a similar genetic makeup. Although the College of Veterinary Medicine dogs have 38 pairs of chromosomes at the University of Illinois–Urbana and humans have 23 pairs, “it’s all the Champaign and suggested she look same genes and they are basically in into it. Terry took her friend’s advice the same order,” Ostrander says. and met with the veterinarians who Not surprisingly, the diagnosis were overseeing the trial program. The and treatment of cancer in dogs and doctors assessed Thunder’s eligibility humans is currently very similar. Dogs and then invited Terry to enroll him frequently get skin, breast, head and in the program. neck, brain, testicular, and abdominal cancers, and veterinarians and veteri- The cancer connection in nary oncologists often employ X-rays, blood tests, biopsies and physical dogs and humans exams to detect cancers and surgery, Cancer is rampant among dogs. chemotherapy, radiation and immu- According to Michael Kastan, notherapy to treat them. Traditionally, executive director of the Duke Cancer these protocols have been the result of Institute, “Cancer kills more than research done on humans. 50 percent of dogs under the age of ten.” Kastan chaired a meeting at the Looking to dogs for clues Institute of Medicine in Washington, D.C., this past June on “The role of This is where the field of compara- clinical studies for pets with naturally tive oncology emerges. The National occurring tumors in translational Cancer Institute started the first formal comparative oncology program cancer research.” He says cancer is PHOTO COURTESY OF PAUL HERGENROTHER similarly widespread in humans, Paul Hergenrother and Timothy Fan of UIUC CONTINUED ON PAGE 12 with dog patient Hoover.

OCTOBER 2015 ASBMB TODAY 11 in humans and dogs. But working with dogs has its disadvantages. Dogs that are enrolled in studies today are only there because their families brought them in. According to Fan, “You can’t order dogs that have cancer.” When starting experiments, cancer can be induced in many mice at the same time, but with dogs, because the cancer occurs spontaneously, the tim- ing of experiments can’t be controlled. “If you are doing an experiment with dogs with cancer with a new drug, you have to have enrollment of the dogs over a longer course of time,” says Fan. PHOTOS OF THUNDER COURTESY OF JEANNEEN TERRY “I can’t control how many dogs are Thunder, whose osteosarcoma was treated with PAC-1, after his amputation. going to come through the front doors CONTINUED FROM PAGE 11 of our veterinary teaching hospital.” Researchers do their best to work in the field in 2003 (see “Sharing is around this limitation by enrolling caring”) and began undertaking com- dogs at multiple recruiting sites that parative studies of naturally occurring are able to participate in the clinical cancers in pet animals and in humans. trials. A few years later, the Comparative Oncology Research Laboratory at Comparing the contrast UIUC was born. Timothy Fan, a comparative oncol- Although dogs and humans ogy researcher and associate professor develop cancers in many of the same at the UIUC’s College of Veterinary ways, there remain interesting differ- Medecine, says, “This discipline is ences that could help to answer some about understanding cancers that are oncology questions. For example, shared between people and dogs and there are lots of similarities between dog and human invasive urinary A tumor grew in Thunder’s left front leg. then developing new therapies that will hold promise in people and dogs.” bladder cancers and how they react to Proponents say studying the canine common chemotherapy treatments. version of the disease may help answer But an interesting difference between questions that have persisted despite the canine and human versions of the studies on mice and humans. One of cancer is the presence of a muta- the main limitations of using mice as tion in the BRAF gene. BRAF is an a model for cancers is that the disease oncogene, and mutation of the gene is not naturally occurring in mice but potentially can cause a normal cell to is induced for the purpose of research. become cancerous. BRAF is common Mice also have a shorter life span, in the diagnosed dogs, but in humans with smaller body size and a different the mutation is usually not present in immunological makeup than humans. urinary bladder cancers but rather in The tiny size of the mice and their melanomas, colon cancer and thyroid associated tumors make them difficult cancer. to analyze repeatedly. In contrast, The effect of the mutation also dogs and humans share similarities in seems to be different in dogs and tumor genetics, recurrence, metastasis humans. BRAF “seems to be a driver and therapeutic response. The syn- mutation present in dogs but not geneic relationships with tumor and in humans,” says Heidi Parker, staff Thunder’s X-ray report revealed osteosarcoma. microenvironment are also consistent scientist at Ostrander’s lab at NHGRI.

12 ASBMB TODAY OCTOBER 2015 “But even if you look at mutations in tolerable dose of oral PAC-1 in human humans, you see the mutations in the cancer patients. It’s too early to say Sharing is caring same pathway, just not in the same what the study results might show. In 2003, Chand Khanna, gene.” At the same time, Fan is conduct- senior scientist at the National Comparative oncology has the ing a clinical trial evaluating the effect Cancer Institute, spearheaded potential to stitch together many gaps of PAC-1 in dogs with brain cancer. the comparative oncology in our understanding of how the can- “The reason why we are pursuing program to help researchers cer develops and how it can be treated. the evaluation in brain cancer is that assess therapeutic treatments for “The fact that the dog has the identi- PAC-1 gets into the brain, which is human cancers by treating pet cal mutation that’s found in many something that is relatively unique,” dogs and cats. Through partici- other kinds of human cancers means says Fan. Therapies that are currently pation in clinical trials, pets can that when we are looking at drugs that available for brain cancer are not very get free, cutting-edge treatments target this mutation, we could see how effective, so “PAC-1 has the ability to for naturally occurring cancers. they react in dogs with bladder cancer meet an unmet clinical need,” adds The NCI also established a versus how they react in humans, say, Fan. national infrastructure called the with colon cancer,” says Parker. Comparative Oncology Trials Main hurdles to overcome Consortium to act as a conduit ”PAC”ing a punch Experts in comparative oncol- between the pharmaceutical A key characteristic of a cancerous ogy are enthusiastic about the field’s industry and research institutes. cell is that it can evade apoptosis, or potential. “It’s an exciting time for The COTC comprises twenty cell death. Avoiding apoptosis makes us,” says Amy LeBlanc, director of academic comparative oncology the cell immortal. Fan and Paul the comparative oncology program centers in the U.S. Hergenrother, a chemistry professor at at the National Cancer Institute. But “The clinical trial infra- UIUC, figured out a way to deal with she notes there still needs to be more structure is unique. The whole the malignant cell’s death-avoiding advocacy to enroll pets into clinical concept of it is to leverage what trick. They discovered a compound trials and to provide better access to we see in naturally occurring dog called procaspase activating com- the genomic data from canine tumors. cancers through the participation pound, or PAC-1, that induces the LeBlanc says getting more funding is of people who seek care,” says activation of procaspase-3 to cas- a pressing challenge, as is creating a Amy LeBlanc, director of the pase-3. Caspase-3 is a protease that canine version of The Cancer Genome comparative oncology program cleaves critical proteins in the cell and Atlas that NCI could host. The dog at the NCI. Academic veteri- eventually triggers apoptosis. As pro- counterpart of the atlas would catalog nary centers and participating caspase-3 is abundant in cancer cells, canine cancer-causing genetic muta- institutes share data as well as “we thought activation of it could be tions in a comprehensive way for expertise. All of the clinical trial very effective and selective for cancer researchers who are using genomics data is added to the system con- cells,” says Hergenrother. and bioinformatics to understand tinuously, and it is proving useful PAC-1 induced death in cancer various forms of the disease in the for drug companies as they work cells when used in a clinical trial in animals. to move drugs forward in human dogs with metastatic osteosarcoma, For pet owners like Terry, compara- clinical trials. a trial in which Thunder is involved. tive oncology has proven helpful and For more information, or to Thunder was treated with oral PAC-1 affordable. Although the osteosarcoma enroll a dog, please visit along with a chemotherapy agent. persists and has spread to his lungs, http://www.caninecancer.com/ After a few weeks, his X-rays “showed Thunder has enough lung capacity to clinicaltrial.html. that two of the smaller tumors were breathe and doesn’t show too many shrinking and the big ones remained signs of respiratory distress. He is thin the same, which is a lot better than but still enjoying his favorite food and getting bigger,” says Terry. drink – sardines and raw goat’s milk. Currently, a phase-1 dose-escalation Terry says she has no regrets about Soma Chowdhury (soma. study of PAC-1 is being conducted in placing Thunder in a clinical drug [email protected]) wrote her stories when she was an intern people with solid tumors or lym- trial. “I know that cancer will lead to at the ASBMB. She is now a phoma at the University of Illinois his ultimate demise, but he will not communications editor at the Cancer Center in Chicago. The goal of have gone without a fight and without National Institute of General Medical Sciences at the study is to evaluate the maximum contributing a little bit to science.” the National Institutes for Health.

OCTOBER 2015 ASBMB TODAY 13 FEATURE Meet Bernhard Küster By Alexandra Pantos

Bernhard Küster at Technische Universität München in Munich, Germany, is a new associate editor of Molecular and Cellular Proteomics. Küster’s research involves studying interactions between drug molecules and protein populations in cells and he is co-founder of the biotechnology firm OmicScouts. ASBMB Today’s science-writing intern Alexandra Pantos interviewed Küster to learn about his research and career trajectory, his position as associate editor, and his work/life philosophies. The interview has been edited for length and clarity.

What is your research and be able to explain potential unde- sired side effects – and also provide group studying? a mechanistic understanding of how We analyze proteomes, with a these molecules work. special emphasis on how drug mol- ecules interact with proteins, signal- Could you describe your ing pathways and entire proteomes. People have realized the idea that one academic background drug only affects one protein is fairly and research training? naive. There are ample examples of I’m a chemist by training. I studied secondary uses of drugs that work by chemistry in Cologne, Germany. Then a different mechanism. We would like I did a Ph.D. in biochemistry at the to understand this more systemati- University of Oxford in the UK and cally, so that, ideally, we measure the postdoc’d at the European Molecular interaction of small molecular drugs Biology Laboratory in Heidelberg with entire proteomes. We use mass- and at the University of Southern spectrometry technologies for that Denmark. That is when I got into because mass spectrometers are the de proteomics. facto standard for detection and quan- tification in proteomics. The reason we are so interested in these drug- Was there one thing that protein interactions is that we would like to find new uses for existing drugs made you choose science?

14 ASBMB TODAY OCTOBER 2015 After finishing school, it was clear nity works by the principle that we all that I was going to study life sci- do something for each other, and the ences, but at the time in Germany better we do that, the better the whole there weren’t so many biochemistry system functions, so it is my turn to university courses. I ended up study- give something back. ing chemistry and then specializing in biochemistry later. My Ph.D. was in How would you say your glycobiology, and to be quite frank, new role is going so far? I ran away from it because it was so difficult. So far, I think it’s going quite well. But at that time, when I had to I read more papers than I did before, make up my mind what would hap- but I also get to see more comments pen to me, I read about early work by from colleagues who have an opinion Matthias Mann and John Yates and about someone’s work. As a reviewer, the like on proteomic measurements. you can just write down your frank I asked Matthias Mann if he was opinion. As an associate editor, you interested in taking me on as a post- have to weigh the arguments. doc. After my postdoc, I spent seven years in the biotech industry. That Do you have any hobbies was from 2000 – 2007, and that was outside of the lab? the early days of big hype in Europe about biotech companies. I got caught I am a keen road biker. Otherwise my family with three kids tends to PHOTO COURTESY OF BERNHARD KÜSTER by that too and joined a proteomics Küster and his road bike. company called CellZome in Hei- keep me busy. delberg, which turned out to be very successful. (Author’s note: CellZome Do you have any advice for is now part of GlaxoSmithKline.) balancing life in the lab Those seven years provided me with quite invaluable experience not only with life outside of the lab? in doing science but also in managing That’s a difficult one, because I like science. I became responsible both working, so I tend to spend a lot of for the mass spectrometry and also time at work. The truth of the matter for the bioinformatics department is that everyone needs to find their in that company. After seven years, I own balance. Some people seem to be had to choose to stay and keep doing able to carry on and on, and it doesn’t what I was doing, take an offer from bother them much. Others need to big pharma, or go back to university watch themselves a little more, because and become an academic with some they may not have that natural ability industry background. And I chose the to keep going. But clearly, it’s impor- latter, because it was the best fit for tant to have something outside of what I wanted to do. work just kind of to restart your brain every now and then. What does the MCP Do you have any words of position mean to you? wisdom for scientists in It’s a very honorable thing to do. I felt flattered these guys thought I was training? worthy of that position. And of course I think it quite useful as a scientist the second reaction was, “Oh God, to try to get rid of one pet hypothesis this is more work!” No, it’s certainly a a day. That keeps your brain alert, or Alexandra Pantos (apantos@ great honor to be asked to serve on the at least you don’t get stuck in a certain asbmb.org) is an editorial way of thinking. assistant and former intern for board of MCP. Any academic commu- ASBMB Today.

OCTOBER 2015 ASBMB TODAY 15 STEAM STEM + ART

Real science gets inked! By Paul Sirajuddin

cientists can be heroic – making Viruses” succeeds in being a comic lasting advances that better peo- work of art, taking readers on a visual S ple’s lives. Comic book creators journey across tundra and space and have historically recognized this and into the ocean and human blood- given scientists their due by turning stream while personifying the viruses, them into superheroes in print. The often as devious and dangerous list of comic superhero scientists and characters. ARTISTS, VIROLOGISTS AND SCIENCE EDUCATORS COLLABORATED TO MAKE science lovers is long, featuring big Neither alive nor dead, viruses “A WORLD OF VIRUSES.” names like Spider-Man, the Invisible are so small they can only be seen Woman, the Black Panther, Iron Man, by powerful microscopes. With the and the Incredible Hulk. But any potential to wreak havoc on food actual resemblance of these costumed supplies and sicken scores of people crusaders to living scientists can be through simple programs of replica- iffy. In the name of entertainment, tion, viruses impact nearly every facet comic books play fast and loose with of human life. the realities of research, discovery and scientists’ actual abilities to control threats to human survival. It’s a bird! It’s a plane! No, it’s a … virologist! Enter “The World of Viruses,” a strikingly illustrated comic book that Judy Diamond is the brainchild of Judy Diamond, professor and curator of informal science education at the University of Nebraska State Museum. An Ameri- can Association for the Advancement of Science fellow, Diamond created a super legion of virologists, sci- ence educators, writers and artists to produce the graphic novel, which pits scientists against viruses in a battle for human survival. Conceived as a new way to increase public understanding about viruses and infectious diseases, “World of Tom Floyd

16 ASBMB TODAY OCTOBER 2015 When Diamond’s team brings them to life, the viruses HPV, foot and mouth disease, HIV, influenza, and Emiliania huxleyi prove to be formidable foes. To make the viruses relatable to an audience, the team has given them humanlike features. This is intended to make it easier, Diamond says, to get readers “to appreciate how things seemed from a virus’s perspec- tive … to get out from a human- centered framework.” In one story, human papillomavi- rus, or HPV, is personified as a crafty, blue-skinned girl wearing a leather jacket and boots. To the reader, she playfully explains that all she desires is a “nice and safe place to live and reproduce” as she slips into a host through a small skin cut. Zipping through arteries and veins, she hides from an army of armor-clad, space- soldier immune cells seeking to destroy her. She reveals how viruses replicate through the host and have turned an Indonesian man into a wart-ridden circus attraction with rootlike growths extending from his hands and feet. (In an actual case study, an Indonesian man working in a carnival sideshow with just such growths was dubbed “the Treeman.”) A U.S. physician arrives on the scene certain he can help the man and explains how HPV caused the Tree- man’s symptoms and how treatments to kill the virus will reverse them. Swarmed and captured by the soldiers, the HPV girl loses her battle with the All comic panels are from “The Curse of the Tree-Man” story in “World of Viruses.” immune system but vows to return. Not all the viruses in the book Weaving science into art are bad. The Emiliania huxleyi virus Supported by a grant from the is a teenage hero in a green hooded National Institutes of Health, Sci- sweatshirt who combats out-of-control ence Education Partnership Awards, E. huxleyi algae blooms that produce Diamond assembled the team behind a gas capable of reflecting sunlight “The World of Viruses” with the help and cooling the planet. In the spirit of of comic book illustrator Tom Floyd. comic supervillains, the untamed algae Author of the online comic Captain bloom erupts from the sea as a giant Spectre, Floyd is a graphic artist and monster, destroying everything in its illustrator for Nebraska Education path. The boy and his virus friends Telecommunications and has worked take small spacecrafts into battle and on “Reading Rainbow” and animated fight the menacing algae, restoring balance to the sea. CONTINUED ON PAGE 18

OCTOBER 2015 ASBMB TODAY 17 and Diamond worked on the scripts, and for “The Curse of the Tree-man,” Floyd brought in Josef Rubinstein, an inker for comic book giants Marvel and DC Comics. As part of the illustrating team, an inker goes over initial pencil drawing outlines with black ink to add depth and dimension to the art. A friend of Floyd’s, artist Scott Beachler, was the colorist, adding, in the final stages, the color, mood and lighting that gives the pages and characters their finished, three-dimensional look. This looks like a job for scientists! “Not compromising the story while keeping the science accurate” was the most challenging aspect of the project, Diamond says. All aspects of the book – characters, stories, and scripts – were run by virologists to make sure the science was sound. It was the first time Floyd and Powell had worked so closely with scientists. The illustrations that bring the stories to life contain clever nods to scientific details. “Specific traits were something we included with each of the characters,” says Floyd. The HPV girl wears an earring that is a graphic representation of the actual virus. The Emiliania huxleyi monster wears wrist- bands that are patterned after the EhV virion structure. Another story on influenza incorporates the shapeshift- CONTINUED FROM PAGE 17 ing nature of the virus by representing it as a villain with an unknowable segments for “NOVA Science Now.” shape that escapes even the scientists. Creating a comic book was no small task for Diamond and Floyd. It required bringing together writers, With great power comes illustrators, inkers and colorists and great responsibility (to finding a way to convey hard science through a medium that traditionally teach science) tells fantastical stories. Recognizing that new and inno- Floyd brought in Martin Powell to vative tools urgently are needed for sci- write the stories. The two had worked entific outreach, Diamond happened together on a comic strip for the upon the comic book idea while look- publisher of “Tarzan.” Diamond and ing for alternative avenues to educate a Floyd developed the characters, Powell young public.

18 ASBMB TODAY OCTOBER 2015 “We wanted to reach teens with information about the science of viruses,” Diamond explains, and “youth librarians advised us that devel- oping comics would be an effective way to reach this goal.” The advice was not unfounded. Interest in comic books is surging, and Diamond Comic Distributors (no relation to Judy) reports comic book sales of $540 million in 2014 – a number that is up from previous years and continues to rise. Carol L. Tilley, a professor of library and information science at the University of Illinois at Urbana-Champaign, maintains that comics are as effective as the most sophisticated forms of literature in teaching kids. In fact, Tilley’s research has found them just as effective as books, if not more (1). Perhaps what is most encourag- ing to Diamond is reader reaction to their particular comic book. “We have lots of anecdotal evidence that kids develop strong attachments to the comics and carry them around in their backpacks. We also know that science teachers are using them in classrooms, because they have requested classroom sets,” she says. Diamond currently is running studies investigating how teachers are using the comics in formal educa- tional settings. She has published a number of peer-reviewed articles on the project (2,3,4), including one looking at the impact of com- writer, West Coast Avengers creator, and Marvel veteran Bob Hall. ics on kids’ interest in science (2). Perhaps researchers and doctors Riding the success of “The World of will again appear as daring heroes on a Viruses,” Diamond is working on a quest for cures, playing into the com- 30-page comic about measles and mon theme of good versus evil that vaccines called “Contagion,” which makes comics hard to put down. In she estimates will be released in a year. the case of real scientists, that theme might just contain some semblance of Paul Sirajuddin (psiraju1@jmhi) Onboard for this project is artist, is a second-year radiation oncol- truth. ogy postdoctoral fellow at The Johns Hopkins School of Medicine. REFERENCES A native of Michigan, he ventured to the East Coast for a postbaccalaurate fellow- 1. https://news.illinois.edu/blog/view/6367/205780 ship at the National Cancer Institute in 2008 2. Spiegel, A.N., et al. Research in Science Education 43(6), 2309 – 2326 (2013). and then earned his Ph.D. from the Georgetown 3. Diamond, J., et al. Curator 58(3), 299 – 311 (2015). University Lombardi Comprehensive Cancer 4. Jee, B., et al. Public Understanding of Science 24(2), 241 – 256 (2015). Center in 2013.

OCTOBER 2015 ASBMB TODAY 19 ANNUAL MEETING

Scientific Symposia: Meet the 2016 plenary lecturers 22 Chemical Biolgy At the 2016 ASBMB annual meeting next spring 22 Bioinorganic Catalysis in San Diego, there will be six plenary lecturers. 23 Lipids and Signaling On the following pages are interviews with those 24 Metabolism, Disease and Drug Design individuals. The interviews were conducted by 25 Nonalcholic Fatty Liver Disease Rajendrani Mukhopadhyay, our chief science 25 Protein Synthesis and Degradation correspondent. The interviews have been edited for 26 Cell Signaling, Kinase and Chemotherapy length and clarity. 27 Glycoscience in Biology 27 System Biology and Proteomics 34 Francis Collins: ‘Now look where we are’ 28 Biochemistry Education 36 Anna Marie Pyle: ‘Trust your own imagination’ 29 Cromatin Organization and Gene Regulation 38 Michael Rosen: Sliding into biology 30 DNA Replication, Repair and Recombination 40 Jared Rutter: Mad about metabolism 32 Recent Advances in Protein Engineering 42 Peter Walter: An explorer of cells 33 Post-translational Modification and the 44 Xiaowei Zhuang: Taking optical microscopy by Microorganism Response STORM

20 ASBMB TODAY OCTOBER 2015 Hope to see you in San Diego!

We invite you to participate in the used to gain new insight into the As always, each symposium 2016 annual meeting of the American functions of novel macromolecular within a theme will incorporate short Society of Biochemistry and Molecu- complexes and their posttranscrip- platform presentations selected from lar Biology, to be held April 2 – 6 in tional or posttranslational the submitted poster abstracts, and sunny San Diego. We have fantastic modifications. will sponsor a poster competition scientific and education programs Excitingly, the 2016 meeting will with cash awards for the winners. planned, as well as workshops in inaugurate a new session — organized Undergraduate and graduate students cutting-edge areas of biochemistry and chaired by graduate students and are especially encouraged to submit and molecular biology and myriad postdoctoral scientists — that will abstracts and to apply for generous networking opportunities. feature lectures by renowned scientists travel awards. The meeting will feature 11 scien- Corey Wilson of Yale, Donald Hilvert The ASBMB annual meeting will tific themes and one theme focused of ETH Zurich, Laurie Read of offer you the atmosphere of a small, on education and professional devel- University of Buffalo, and Feng Schao specialized conference organized by opment, with lectures from the most of the National Institute of Biologi- themes and moreover provide you prominent scientists in biochemistry cal Sciences, Beijing, China. The new with opportunities to learn from and and molecular biology. Several of the session will include opportunities interact with scientists outside of your themes represent traditional areas of for other student and postdoctoral research area. Furthermore, in con- interest within the ASBMB member- scientists to speak on topics related to junction with the 2016 Experimental ship, such as gene regulation and protein engineering and post-transla- Biology conference, you will have chromatin modification, enzyme tional modifications. an unparalleled opportunity to learn catalysis, protein synthesis and degra- Indeed, the 2016 annual meet- about the latest discoveries in every dation, and lipids and lipid signaling. ing will engage scientists at all levels facet of biology. However, new and emerging fields within the ASBMB membership. Your participation will be rewarded also are featured, such as systems biol- Moreover, in addition to lectures with exposure to great science, oppor- ogy and metabolic networks, glycosci- delivered by our award winners, ple- tunities to establish collaborations and ence, and the development of new nary lectures will be given by Francis to network, and access to mentoring chemical tools to interrogate biologi- Collins of the National Institutes of and career advice. We promise not cal questions in vivo. Themes that will Health; Anna Pyle of Yale University only wonderful science but also awe- pervade many of the symposia will be and the Howard Hughes Medical some weather! Submit your abstracts the molecular basis of disease; how Institute; Michael Rosen of the Uni- today and prepare yourselves for a the development of new techniques versity of Texas Southwestern Medical fascinating experience! facilitates a more detailed understand- Center and HHMI; Jared Rutter of Squire J. Booker, ing of biomolecules like DNA, RNA, the University of Utah and HHMI; Pennsylvania State University and proteins, lipids and carbohydrates and Peter Walter of the University of Cali- Howard Hughes Medical Institute how they interact with each other; fornia, San Francisco, and HHMI; Wei Yang, and how the enormous bodies of and Xiaowei Zhuang of Harvard National Institutes of Health genomic, proteomic and molecular University and HHMI. (Read Q&As 2016 program co-chairs and cellular imaging data are being with them starting on page 32.)

OCTOBER 2015 ASBMB TODAY 21 Abstract submission deadline: Nov. 5

CHEMICAL BIOLOGY Next-generation opportunities By Erin Carlson & Joseph Jez

Discoveries often happen in the gaps tion warned of a coming post- communication to control biological between disciplines, and, with the antibiotic era resulting from the responses. These inputs and responses world’s population projected to grow spread of resistance to antimicrobials. occur inside cells and across the envi- from 7 billion to 9 billion by 2050, The first session will examine how ronment. New approaches for visual- the next generation of chemists and chemical biologists are using new izing and manipulating metabolic and biologists will use those discoveries to strategies for antibiotic discovery and cellular systems will be the focus of tackle new challenges. These chal- for understanding resistance the third session. lenges include controlling microbial mechanisms. infections, improving food produc- Chemistry, biology tion, understanding cellular com- munications and managing global The greening and sustainability sustainability. Chemists and biologists of chemical biology The challenges of global sustainability approach these fundamental questions Although chemical biology has its are wide-ranging and complicated. armed with vast genomic information, roots and many successes in biomedi- But there are rich, new opportunities powerful analytical tools and an eye cine, its application to plants is just for the application of chemistry and toward solving real-world problems. beginning. The second session will biology to these challenges. This final This 2016 American Society for highlight how the interplay of chemis- session will showcase how advances Biochemistry and Molecular Biology try and biology is advancing knowl- in biocatalysis and systems/pathway annual meeting symposium will high- edge both of how plants grow and of engineering are aiming to meet these light research that crosses the bound- the biosynthesis of pharmaceutically problems. aries between chemistry and biology important molecules. and explores new applications and ORGANIZERS: opportunities for chemical biology. Erin Carlson, Chemical communication, University of Minnesota, The postantibiotic era biological regulation and Joseph Jez, Washington University in St. Louis. Last year, the World Health Organiza- All organisms use small molecules for

BIOINORGANIC CATALYSIS A closer look under the hood By Vahe Bandarian & Carsten Krebs

Enzymes are the sophisticated about enzymes. In the four sessions of Many enzyme-catalyzed reactions are molecular machines that catalyze this symposium, our invited speakers chemically difficult, yet proceed with myriad biochemical reactions occur- will take the audience on a tour of the ease in ambient conditions. Typi- ring in nature. For nearly a century, forefront of enzyme research, offering cally, such reactions involve highly a large body of research has provided a look under the hood of some of the reactive intermediates that activate a wealth of insight into enzyme- most sophisticated enzymes. the substrate at a specific, often catalyzed reactions and allowed us to inert, position. What is perhaps most learn a tremendous amount about remarkable about such enzymes is the how enzymes function. Despite this, Metalloenzymes and fact that the enzyme scaffold controls there is still a lot to be unraveled radicals in catalysis and directs the reactivity by suppress-

22 ASBMB TODAY OCTOBER 2015 www.asbmb.org/meeting2016

ing side reactions. Two sessions will quantum leap in the understanding of a snapshot of the enzyme in its stillest be devoted to enzymes that catalyze its inner workings, yet many enzymes form. In reality, enzymes are dynamic chemically-demanding reactions cannot be crystallized readily due to and constantly in motion. One session involving reactive intermediates. The their size or stability. This session will will be devoted to research that takes sessions will focus on highly reactive focus on the structural biology of our understanding of enzyme catalysis bioinorganic and bioorganic enzyme such complex enzymes to highlight from the level of static pictures to the reaction intermediates, such as high- the role of structure in the function of next level by examining the role of valent metal-oxo species or organic complex enzyme systems. enzyme dynamics in catalysis. radicals.

Enzyme dynamics and ORGANIZERS: Structural studies of enzyme motions Vahe Bandar- ian, University complex systems Although knowledge of the three- of Arizona, and Knowledge of the three-dimensional dimensional structure of an enzyme is Carsten Krebs, structure of an enzyme has provided a immensely valuable, it provides only Pennsylvania State University.

LIPIDS AND LIPID SIGNALING Lipids continue to surprise us By James Ntambi &Tobias Walther

It has become increasingly clear that physiological functions of membrane nuclear and G-protein–coupled recep- lipids play key roles as structural, contact sites. tors as paradigms. The presentations signaling and regulatory molecules. will extend to cover the key roles of Understanding pathways of lipid Lipid membrane regulation some signaling lipids in obesity and metabolism regulation is fundamental diabetes. Maintaining membrane homeostasis to deciphering how cells and organ- is important for cellular organization isms grow, develop and respond to and integrity. In this session, leaders Lipids and energy external stimuli. Four sessions of in the field will present the impor- American Society for Biochemistry metabolism tance of post-translational regulation and Molecular Biology 2016 annual Neutral lipids are essential to the of phosphatidic acid and phos- meeting in San Diego will feature storage of metabolic energy. The final phoinositide metabolism enzymes leaders in the research of lipid func- session will highlight advances in the in maintaining lipid homeostasis. tion in health and disease. understanding of cellular lipid storage Attendees also will hear the latest mechanisms. It will provide insights Membrane contact sites on the transcriptional regulation of into synthesis and regulation of fatty lipid metabolism by sterol regulatory acids, their desaturation, and how and lipid trafficking element-binding proteins, or SREBPs. these mechanisms affect whole-body Recent breakthroughs in cell biology energy metabolism as well as insulin highlight that many cellular organ- Lipid signaling signaling. elles are in tight, molecular contact. Signaling lipids control many cellular ORGANIZERS: A major, emerging function of these processes, including cell growth, James Ntambi, organellar contact sites is transport of apoptosis and metabolism. This ses- University of lipids. The first session will high- sion will feature the diverse signaling Wisconsin-Mad- light the molecular architecture and mechanisms of lipids, focusing on ison, and Tobias Walther, Harvard University.

OCTOBER 2015 ASBMB TODAY 23 Abstract submission deadline: Nov. 5

METABOLISM, DISEASE AND DRUG DESIGN Drug discovery and the changing landscape of biology By Clifton Barry & John Kozarich

The ultimate goal of most scientists the proteome in normal and disease of naturally occurring analogs have who work in biological chemistry is to states. the potential to transform the field. understand and affect human health. Integrating natural products with As our understanding of biological Mechanism matters structural biology and detailed mecha- processes at both the macroscopic and nistic understanding provides new molecular levels increases in complex- The second session will consider how hope for exploiting naturally evolved ity, new approaches and concepts biochemical insights into processes as antibacterials against humankind’s rapidly feed into drug-discovery basic as protein synthesis provide new most ancient diseases. programs, producing new tools that guide posts for innovative approaches further inform our understanding in to treating disease. Pathway-driven A thousand words an iterative way. Drug discovery is an genetic methods of understanding The final session will dig into how early adopter of biochemical innova- druggability can take a lot of the modern imaging methodologies tion, and this 2016 American Society guesswork out of target selection. accelerate understanding of complex for Biochemistry and Molecular systems, diseased or normal. Imag- Biology annual meeting symposium And bringing together a detailed ing mass spectrometry now allows will highlight some of the approaches understanding of the enzymology unparalleled understanding of small being taken to engage the most recent and mechanism of neurodegenerative molecule distribution and spatial advances in biochemistry and molecu- diseases rapidly is advancing thera- localization in tissues. Activity-based lar biology. peutic approaches using the tools of imaging promises to transform patho- structure-based design. gen detection. Whole-body imaging Big data: adding -omics using positron emission tomography, The front line of contemporary Natural beauty: or PET, and computed tomography, -omics is moving beyond transcripts or CT, routinely is used clinically, but and proteins to the more analytically harnessing evolution new generations of probes built on demanding tasks of quantifying lipids Natural products are fascinating understanding the biochemistry of and metabolites. The first session will examples of evolutionary master- disease are potentially transformative. highlight these advances and their pieces, often perfectly fit for their integration with the blueprints (DNA natural niche. The third session will ORGANIZERS: and RNA) and effectors (protein). It discuss how chemically modifying Clifton Barry, National Institutes also will consider how activity-based these works of natural art often is of Health, and probes applied in cell or tissue lysates daunting, but new metagenomic John Kozarich, have accelerated our understanding of approaches to identifying families ActivX Biosciences Inc.

24 ASBMB TODAY OCTOBER 2015 www.asbmb.org/meeting2016

NONALCOHOLIC FATTY LIVER DISEASE What’s the skinny? By David D. Moore & Marion Sewer

Currently afflicting more than 30 in the development and progres- spawned the need for a multipronged percent of the U.S. population, nonal- sion of NAFLD. Understanding the therapeutic approach including the coholic fatty liver disease, or NAFLD, prominent role that nuclear receptors use of mitochondrial protonophores. rapidly has emerged as a major play in the transcriptional program epidemic. Although the disease is dis- that underlies varied disease states Metabolic insight into proportionately prevalent in Hispanic including NAFLD has led not only to Americans, increasing incidences in new information about the molecular the enzymatic players India and Brazil highlight its global mechanisms behind hepatic dysfunc- Multiple hepatic enzymes, including impact. NAFLD is the most common tion but also to considerations for an fatty acid elongases and thioesterases, cause of liver failure and transplan- attractive therapeutic strategy. coordinately regulate lipid homeosta- tation and the most prevalent liver sis. Consequently, aberrant catalytic disorder in industrialized nations, Genetic determinants and activity of these lipid metabolic and it is linked to the development enzymes has been shown to confer of type 2 diabetes, cardiovascular extrahepatic complications alterations in fatty acid concentra- disease, dyslipidemia and metabolic Population-based studies and exome- tions that are causally linked to syndrome. Three sessions at the 2016 wide association studies have enabled NAFLD. Finally, mounting evidence American Society for Biochemistry researchers to uncover genetic variants has established a prominent role of and Molecular Biology annual meet- that confer susceptibility to NAFLD. branched-chain amino acid metabo- ing will provide an update on the These studies, coupled with investi- lism in multiple pathophysiologic signaling pathways that contribute to gation into the role of fetal hepatic states including the hepatic dysfunc- hepatic dysfunction and NAFLD and inheritance in the development of tion that contributes to the etiology of insight into the genetic determinants metabolic diseases in the offspring NAFLD. that contribute to the etiology of the of obese parents, have increased disease. our understanding of the complex molecular mechanisms that under- ORGANIZERS: David D. Moore, Hepatic lipid signaling lie NAFLD. Significantly, NAFLD Baylor College increases susceptibility to other The JNK and hedgehog signaling of Medicine, and metabolic disease states, which has Marion Sewer, pathways have become pivotal players University of California, San Diego.

PROTEIN SYNTHESIS AND DEGRADATION Shifting paradigms in the regulation of protein functions By Christine Dunham & Yihong Ye

Until the discovery of ubiquitin-medi- and temporal regulation of protein autophagy pathway. This 2016 Ameri- ated proteolysis in the 1980s, central functions can be achieved either can Soceity for Biochemistry and dogma dictated that protein transla- during translation or by controlled Molecular Biology annual meeting tion was the point of functional regu- proteolysis through the proteasome lation. Now it is believed that spatial or the more recently characterized CONTINUED ON PAGE 26

OCTOBER 2015 ASBMB TODAY 25 Abstract submission deadline: Nov. 5

CONTINUED FROM PAGE 25 ing or extra pieces. The cell faces a unconventional mechanisms. similar problem when it comes to the theme will consider how, as new tools expression of giant protein complexes, and methods are developed, unantici- Why it takes so many such as the proteasome and nuclear pated paradigms are being formed in pore complex. The second session will proteins to destroy one this complex and exciting field. explore the emerging mechanisms the The proteasome and autophagy cell uses to build complex molecular systems are surprisingly complex as A new paradigm in machines. exemplified by the large number of translation regulation regulators required to destroy a single protein molecule. The last session’s RNA makes up the functional centers The good, the bad discussion will center on how these of the ribosome and is the building and the ugly regulators cooperate and why a cell block of its enzymatic activity. The The cell handles critical regulation and a multicellular organism need so first session will explore how differ- of protein functions through diverse many of them to maintain fitness. ent types of RNA regulate protein quality control programs, licensing synthesis. only “good” polypeptides to func- ORGANIZERS: tion while sentencing “bad” ones for Christine LEGO them up Dunham, Emory destruction. The third session will University, Building with LEGOs often involves focus on newly discovered quality and Yihong Ye, dealing with misassembled, miss- control pathways as well as National Institutes of Health.

CELL SIGNALING, KINASE, AND CHEMOTHERAPY New concepts from bench to bedside By Dan Leahy & Susan Taylor

Kinase-mediated signaling plays essen- such events influence kinase activ- New strategies for designing kinase tial roles in cell growth, differentia- ity. The first session will highlight inhibitors are discussed in terms of tion and homeostasis. Kinases signal new insights into the molecular pseudokinases, active kinases and by switching between “on” and “off” mechanisms governing the activity allosteric sites. In the third session, states, and many inputs regulate the of key kinases, how the activity of new approaches for discovering target activity of each specific kinase. Abnor- these kinases becomes deregulated in genes will be described as will new tar- mal kinase activity, often the result disease and how an understanding of gets that lie downstream of kinases. of mutation, is associated with many mechanism has influenced strategies cancers, and kinase inhibitors have to target kinases therapeutically. New roles for old kinases become a highly successful and grow- Kinases are dynamic molecular ing class of anti-cancer agents. This Spatiotemporal control switches that easily can be hijacked to 2016 American Society for Biochem- Movement of kinases both within create oncogenes that drive cancers. istry and Molecular Biology annual membranes and to and from different The final session will discuss how both meeting symposium will focus on membrane compartments is known to kinases and pseudokinases can drive emerging insights into the molecular affect the nature and timing of kinase tumors and introduce new roles for mechanisms by which kinase activity signaling. The second session will PKC and PKA as tissue-specific tumor is regulated and how these insights are highlight state-of-the-art studies of the drivers and tumor suppressors. influencing strategies to target kinase movement of specific kinases during activity in cancer. signaling and how location modulates ORGANIZERS: Dan Leahy, Johns signaling activity. Hopkins University Molecular mechanism School of Medi- Intra- and intermolecular interactions, cine, and Susan phosphorylation and combinations of Therapeutic strategies Taylor, University of California, San Diego.

26 ASBMB TODAY OCTOBER 2015 www.asbmb.org/meeting2016

GLYCOSCIENCE IN BIOLOGY From humans to bacteria By David Vocadlo & Lance Wells

Carbohydrates are the only one of The first session will highlight the The power of the four major biomolecules of life structurally simple yet influential chemical biology that modifies the other three. This is O-GlcNAc modification that modifies hundreds if not thousands of nuclear, The third session will highlight the perhaps unsurprising, since glyco- mitochondrial and cytosolic proteins. power of chemical biology approaches sylation is well suited for increasing While O-GlcNAc has been associ- in glycoscience. Topics to be covered the functional diversity of resulting ated with myriad biological functions, include recent findings regarding glycoconjugates. The various mono- this session will focus on the emerg- comparative and competitive activity- saccharides found in glycans, coupled ing role of O-GlcNAc in regulating based glycosidase profiling, cotrans- with the variability in how they are gene expression. Talks will cover how lational addition of O-GlcNAc to O-GlcNAc contributes to regulation proteins and the use of photoprobes attached to each other, confers onto of RNA Pol II and ChREBP as well to investigate protein glycosylation glycans incredibly high informa- as how mutations in OGT associated within the secretory pathway. tion content that is reflected in their with X-linked intellectual disability, or diverse structures and topologies. This XLID, impact the transcriptome. Glycan complexity 2016 American Society for Biochem- The final session will cover the istry and Molecular Biology annual Structural and structurally complex glycans found in meeting symposium will focus on enzymological advances bacterial glycosylation and the micro- how glycosylation impacts biology biome. Recent data regarding glycan- The second session will crystallize dependent interactions between host and how technological advances are recent advances gained primarily gut and bacteria including pathogenic providing novel insights into the roles by structural biology and enzymol- processes will be described. of glycans in basic cellular processes ogy approaches with carbohydrate and pathophysiologies. processing enzymes. New molecular ORGANIZERS: insights into how glycosidases and David Vocadlo, The emerging role glycsyltransferases recognize and Simon Fraser processes varied glycoconjugates will University, British of O-GIcNAc be discussed. Columbia, and Lance Wells, University of Georgia.

SYSTEMS BIOLOGY AND PROTEOMICS The molecular linguistics of biological systems

Understanding a complex biological the next bottleneck of this learning with computational modeling. In this system, be it a single cell, multicellular process is mapping meaningful com- 2016 American Society for Biochem- organism or multispecies consortia, binations of individual “words”— that istry and Molecular Biology annual requires understanding its language: is, active components. This challeng- meeting symposium, experts from its means of functional communica- ing endeavor requires integration of these intersecting fields will enlighten tion between numerous individual high-throughput experimental plat- components. In a post-genomic era, forms (most importantly, proteomics) CONTINUED ON PAGE 28

OCTOBER 2015 ASBMB TODAY 27 Abstract submission deadline: Nov. 5

CONTINUED FROM PAGE 27 ing appreciation of an intricate web to dissect structural and functional of molecular interactions driving dynamics of protein machines and to us as to how to decode the language of each living cell. Cellular networks understand their action mechanisms. molecular complexes and interactions of various types (metabolic, signal- in various biological systems. ing and regulatory) contain broadly Molecular crosstalk conserved as well as unique aspects, between species Where proteomics which together comprise a subject of adaptive evolution. Recent progress in The final session will take us to the meets medicine network modeling yields new insights next layer of molecular interactions: Proteins are undoubtedly the most into the linguistics of biological between cells of different types and informative class of biomolecules in systems. even different species (as in environ- biomedical research not only due to mental or host-associated microbial their direct biological relevance to The sociology consortia). Recent progress in this human pathologies but also as major of protein machines rapidly expanding field heavily relies drug targets for many diseases. The on next-generation meta-omics tech- next generation of mass spectrometry Protein complexes are macromolecular nologies as well as on new approaches enables systematic analyses of human machines that coordinate the func- to systems-level data analysis and proteomes for improved disease diag- tions of the cell. These functional predictive modeling. nostics and treatments. modules are dynamic entities whose relationships are orchestrated carefully ORGANIZERS: Lan to maintain cell homeostasis. Inno- Huang, University Networking in the cell of California, vations in mass spectrometry-based Irvine, and Andrei The explosion of Web-based social approaches have made it possible Osterman, San- networks coincided with our grow- ford Burnham Prebys Medical Discovery Institute.

BIOCHEMISTRY EDUCATION Training the next generation of biochemists and molecular biologists By Celeste Peterson & Margaret Carroll

Nobelist Sir William Lawrence Bragg molecular biology, engage students on first session will present some proven once said, “The important thing in both a theoretical and an experiential pedagogical strategies to stimulate science is not so much to obtain new level, and prepare them for a range of student interest and meet the com- facts as to discover new ways of think- science, technology, engineering and petencies of today’s biochemistry and ing about them.” This quote raises math careers. molecular biology education. These the question of how today’s educators include using threshold concepts to should structure training programs so Leading the way in the scaffold student learning, improving that students maintain their sense of quantitative thinking about molecular wonder about the world both in and undergraduate classroom: dynamics and integrating research into out of academia. The 2016 American Depth, breath or a totally BMB courses. Society for Biochemistry and Molecu- different approach? lar Biology annual meeting educa- Graduate and postdoc tion and professional development Biochemistry can be daunting, and, training: Ensuring the symposium explores how programs while a thorough understanding of can offer a deep and quantitative foundational principles is essential, attainment of rewarding concepts often are obscured by a understanding of biochemistry and thick layer of details and jargon. The STEM careers

28 ASBMB TODAY OCTOBER 2015 www.asbmb.org/meeting2016

The National Institutes of Health Prepping for the MCAT The molecular world is too small for and other agencies are supporting the naked eye to see. The last ses- programs that encourage a much The content and goals of the MCAT sion will focus on how new tools in broader definition of graduate student changed dramatically in 2015, with three-dimensional printing, animation and postdoc training. The second a renewed focus on biochemistry and software and social media are helping session will discuss the importance the social sciences. The third session students to better see what’s going on of individual development plans, or will examine the first year’s perfor- in cellular biochemistry and molecular IDPs, and examine how they enhance mance of the MCAT 2015, provide biology. opportunities for both academic and curriculum ideas on preparing for nonacademic STEM careers while medical school and discuss the role of allowing participants to maintain physicians in today’s biomedical health ORGANIZERS: care system. Celeste Peterson, the focus necessary to complete their Suffolk University, dissertations or postdoc research com- and Margaret mitments. You’ve got to see it Carroll, Medgar to believe it Evers College, City University of New York.

CHROMATIN ORGANIZATION AND GENE REGULATION Making sense of genetic switches By Joan Conaway & Bing Ren

As part of President Obama’s Precision gene regulation. The development Transcriptional Medicine Initiative, researchers will of high-throughput technologies for gather genomic, transcriptomic and defining chromatin structure and regulatory mechanisms other data from a cohort of a million organization, the identification of Many transcription regulators have volunteers. Will we have the ability potential cis-regulatory sequences at been identified over the past two to interpret the enormous amount of a genomic level, and the discovery of decades. But much remains to be information that will emerge from roles for noncoding RNAs in chroma- learned about the molecular mecha- this effort? In particular, will we be tin remodeling and gene regulation nisms by which they work together to able to define the significance of dif- have facilitated this paradigm shift. control transcriptional output during ferences that occur between individu- Our symposium for the American normal development and cellular als and that could predispose a person Society for Biochemistry and Molecu- function and during disease states. to one of many diseases that contain a lar Biology 2016 annual meeting will Presentations in this session will high- genetic component? The answers will make sense of these developments and light how mutations in components depend in large part on our under- consider the intimate links between of the basic transcription machinery standing of the mechanisms of gene transcription regulation, genomic give rise to developmental disorders regulation. stability and human disease. and cancer. Also addressed will be our In the time since Jacob and increasing appreciation of the cross- Monod first proposed the concept talk between transcriptional regula- of transcriptional regulators and Chromatin organization tion and DNA repair processes. cis-regulatory sequences 55 years How are chromosomes organized in ago, the field of gene regulation has the nucleus? How does chromatin Chromatin remodeling undergone a series of important organization affect gene regulation in developments. Among these are an eukaryotes? With the rapid advances and epigenetics ever greater understanding of the in sequencing-based technologies for The third session will focus on mecha- enzymes and proteins that shape chro- mapping chromatin organization, the nisms of epigenetic regulation. DNA matin architecture and the realization answers to these questions are emerg- methylation is a well-established that three-dimensional chromatin ing and will be addressed in the first epigenetic mark with important roles architecture is involved intimately in session. CONTINUED ON PAGE 30

OCTOBER 2015 ASBMB TODAY 29 Abstract submission deadline: Nov. 5

CONTINUED FROM PAGE 29 will be a focus of this session. ing RNA transcripts. A variety of such RNA transcripts have been character- in gene regulation. Emerging evidence Noncoding RNA ized and linked to gene regulation, that methylation of mRNAs and other and gene regulation and these will be featured in the transcripts also can have an impact on fourth session. regulatory processes will be discussed. With most of the human genome transcribed into RNA during at least Understanding mechanisms responsi- ORGANIZERS: ble for epigenetic regulation via chro- some stage of development, a major Joan Conaway, matin requires a detailed knowledge challenge is to understand the biologi- Stowers Institute of histone chaperones and chromatin cal functions, where they exist, of the for Medical plethora of newly identified noncod- Research, and remodeling enzymes, and these also Bing Ren, University of California, San Diego.

DNA REPLICATION, REPAIR AND RECOMBINATION Make no mistake about it By James Berger & Agata Smogorzewska

Every human cell contains roughly many aspects of this critical event and mechanistic insights into the two meters’ worth of DNA. As a con- using purified components in a test fundamental processes that cells use to sequence of this great length, over the tube. The growing lines of evidence recognize and repair mistakes. Mecha- course of an average human lifetime, also point to sophisticated mecha- nisms for cutting and pasting entire the body will have synthesized enough nisms that tightly control replication DNA segments, such as occurs during DNA to reach about halfway to the termination. transposition, also will be discussed. nearest star, two light-years away! How cells manage to make this extraordi- How do you use your What happens when nary amount of DNA while avoiding errors that can lead to mutation and sister to repair yourself? replication proceeds disease remains one of the foremost During and immediately after DNA through a difficult terrain? questions in molecular biology. This replication, cells have an option of In the final session, we will discuss 2016 American Society for Biochem- repairing mistakes using the just- what happens when replication forks istry and Molecular Biology annual duplicated sister chromatid to avoid become stressed or stall at roadblocks, meeting theme will focus on how permanent changes to the genetic such as damaged bases, nicks or cova- DNA replication, repair, and recombi- material. In the second session, we lent crosslinks. Along the way, we will nation is done right. will discuss how recombination-based sneak in some discussion of chromatin repair is regulated in the presence and and examine what happens to histones First things first absence of a sister. DNA gymnastics, during replication and repair. anyone? In the first session, speakers will discuss how the process of replication is initiated and terminated properly. Fix it up ORGANIZERS: Although replication initiation is A veritable hive of proteins swarms James Berger, around DNA, looking for mistakes Johns Hopkins extremely complex, we now know School of Medi- enough about the players and their and patching them up. The third cine, and Agata regulation to be able to recapitulate session will highlight recent structural Smogorzewska, The Rockefeller University.

30 ASBMB TODAY OCTOBER 2015 Attention grad students and postdocs

Reasons to attend Events • Present your research: oral and poster • Professional-development event to learn presentations available about different career paths, present your • More than 200 travel awards of $1,000 each research and network with colleagues are available to grad students and postdocs • ASBMB Game Night, a new networking • New professional-development events for and social event grad students and postdocs • Scientific sessions organized by grad students and postdocs Important dates • Workshop and scientific sessions • Abstract submission deadline: Nov. 5 on teaching undergraduates. • Travel award application deadline: Nov. 12 • Workshop to develop competitive • Early registration deadline: March 1 broader impacts statements for those • Learn more and submit your abstract: applying for NSF awards www.asbmb.org/meeting2016/ • Workshop to improve science communication skills through storytelling • Dedicated networking event for women scientists

OCTOBER 2015 ASBMB TODAY 31 STRAIGHT FROM THE BENCH: 2016 ANNUAL MEETING SESSIONS LED BY GRAD STUDENTS AND POSTDOCS

www.asbmb.org/meeting2016

Biofuels Production Proteins for Energy Generation and Storage

It’s not easy It’s electrifying! Living in a being green material world

Organizers: Biopolymers Production Proteins in Materials Design Bioremediation Biofuels Production Biopolymers Production

Michael White Danielle Schmitt University of Maryland, Baltimore County Doctor, doctor, You’ve gotta Recent Advances in give me the news find a method Complex assemblies and Machines Methods of Protein Protein Engineering Engineering San Diego Marriot Marquis Hotel Engineered Proteins as or Predictive Modeling Tuesday Evening, April 5, 2016 to Make Therapeutics

You’re motoring

Complex assemblies and Machines Molecular Motors Dr. Donald Hilvert, Dr. Corey Wilson, ETH Zurich Yale University Session Keynote Speakers

Grad/Postdoc first authors submitting abstracts to topics for this session will be considered for short talks and must also present posters. All others will be programmed for poster presentation. Topic categories are #2100-2110. Abstract submission deadline: Nov. 5th

Doctor, doctor You’ve gotta find a method It’s electrifying! Engineered proteins show great promise in Developing novel proteins requires knowledge Much debate surrounds the future of energy, be medical applications. These categories of current engineering techniques. These it generation, transfer, or storage. These topics focus on how engineered proteins and protein categories focus on methods and predictive center on how engineered proteins can be scaffolds can be used as therapeutics. modeling for protein engineering. used in various energy applications.

You’re motoring It’s not easy being green Living in a material world The grunt work of a cell is performed by Many environmental issues that arise today can Many of the products that surround us molecular machines, these systems can be mitigated by “green” technologies. everyday are made possible by advances in also be used ex cellulo to create or power Protein engineering has a large potential for materials science. These categories pertain products. These topics touch on the utility of employment in the green revolution, as to the application of protein engineering in engineered assemblies. discussed here. material products.

32 ASBMB TODAY OCTOBER 2015 STRAIGHT FROM THE BENCH: 2016 ANNUAL MEETING SESSIONS LED BY GRAD STUDENTS AND POSTDOCS

www.asbmb.org/meeting2016

Biofuels Production Proteins for Energy Generation and Storage

It’s not easy It’s electrifying! Living in a being green material world

Organizers: Biopolymers Production Proteins in Materials Design Bioremediation Biofuels Production Biopolymers Production

Michael White Danielle Schmitt University of Maryland, Baltimore County Doctor, doctor, You’ve gotta Recent Advances in give me the news find a method Complex assemblies and Machines Methods of Protein Protein Engineering Engineering San Diego Marriot Marquis Hotel Engineered Proteins as or Predictive Modeling Tuesday Evening, April 5, 2016 to Make Therapeutics

You’re motoring

Complex assemblies and Machines Molecular Motors Dr. Donald Hilvert, Dr. Corey Wilson, ETH Zurich Yale University Session Keynote Speakers

Grad/Postdoc first authors submitting abstracts to topics for this session will be considered for short talks and must also present posters. All others will be programmed for poster presentation. Topic categories are #2100-2110. Abstract submission deadline: Nov. 5th

Doctor, doctor You’ve gotta find a method It’s electrifying! Engineered proteins show great promise in Developing novel proteins requires knowledge Much debate surrounds the future of energy, be medical applications. These categories of current engineering techniques. These it generation, transfer, or storage. These topics focus on how engineered proteins and protein categories focus on methods and predictive center on how engineered proteins can be scaffolds can be used as therapeutics. modeling for protein engineering. used in various energy applications.

You’re motoring It’s not easy being green Living in a material world The grunt work of a cell is performed by Many environmental issues that arise today can Many of the products that surround us molecular machines, these systems can be mitigated by “green” technologies. everyday are made possible by advances in also be used ex cellulo to create or power Protein engineering has a large potential for materials science. These categories pertain products. These topics touch on the utility of employment in the green revolution, as to the application of protein engineering in engineered assemblies. discussed here. material products.

OCTOBER 2015 ASBMB TODAY 33 ANNUAL MEETING

PLENARY LECTURER ‘Now look where we are’ By Rajendrani Mukhopadhyay

Francis Collins doesn’t need an introduction nity to achieve remarkable advances at to the biomedical research community. Before this exceptionally promising time in he became the 16th director to take the helm of scientific history. the 27 institutes and centers that make up the National Institutes of Health in 2009, Collins There is a perception served as director of the NIH’s National Human Genome Research Institute from 1993 to 2008 among scientists that and led the NIH’s Human Genome Project. The the NIH is focusing more project culminated in April 2003 with a reference on translational than on sequence of human DNA. Prior to his tenure at the NIH, Collins was a fundamental research. Howard Hughes Medical Institute investigator at What are your thoughts on the University of Michigan, where his team was well known for discoveries of disease genes, such as the one for cystic fibrosis. that perception? He is a member of the Institute of Medicine and the National Academy of Sci- I’m concerned about that percep- ences, won the Presidential Medal of Freedom in November 2007 and received tion. I certainly feel strongly that the National Medal of Science in 2009. much of our success over the decades As someone very much at ease in talking about science to the general public, has been in the basic science arena. Collins has made numerous media appearances, including on “The Colbert When we use our standard coding Report” when it was on the air, and joined the Rock Stars of Science to promote scheme to catalog NIH’s investments, bench-to-bedside research by performing with Aerosmith’s Joe Perry. Collins also about 53 percent is basic, and 47 per- has written five books, three on the intersection of science and faith, one on the cent applied, and that balance has not principles of medical genetics, and another on personalized medicine. changed significantly in decades. Some would argue, however, that when you look at what we call basic The NIH is due to send a science, some of it is not quite as basic of scientific opportunity and public- as it used to be. More of NIH-sup- five-year strategic plan to health need. (The plan) will also talk Congress at the end of this about stewardship and the importance year. What are you hoping that NIH attaches to making sure that every dollar that we receive from to put in that plan? Congress is thoughtfully applied in a The goal is to lay out in broad way that will ultimately produce the strokes what an exciting time this is most useful results. We will include for biomedical research. There will be comments on such things as rigor and a particularly strong case made for the reproducibility. The plan will refer importance of fundamental science, prominently to the strategic plans of which undergirds everything we’ve the 27 institutes and centers. We’re ever achieved and will achieve. not trying to replicate all of the things (The plan) will also explain how we that they have already outlined. This set priorities, because Congress and will be more of an overarching per-

the public are often puzzled about spective of how the whole NIH works PHOTO COURTESY OF NATIONAL INSTITUTES OF HEALTH that. The process is a complex mix together with the scientific commu- Collins and CNN’s Sanjay Gupta earlier this year.

34 ASBMB TODAY OCTOBER 2015 ported basic science Has your own now has a connection to a possible disease scientific application. Some of thinking been that evolution reflects the way in which changed by science is moving for- being NIH ward. We are learning director? more about molecules and pathways in a way Dramatically. We’ve that attaches them to gone from science insights about disease. that, by necessity, had I want to, however, to be focused on a assure basic scientists limited snapshot of that we talk about what was going on in this situation a lot at biology to approaches NIH. We’ve looked to that allow you to ask see how basic science questions that are grant applications much more compre- score in review and hensive, with the word they actually do better, “all” in them. Just as on the average, than an example, my own translational grant lab at NIH is pursu- applications. ing explanations of You know what the ways in which I think the main genomewide chroma- problem is? Everybody PHOTO COURTESY OF NATIONAL INSTITUES OF HEALTH tin structure within is really stressed right NIH grantee Rudy Tanzi, Collins, and Aerosmith’s Joe Perry, at “Rock Stars of Science” pancreatic islet cells event on Capital Hill in 2009. now. NIH has lost confers understand- almost 25 percent of things changed there? ing about diabetes its purchasing power over the last 12 risk. That approach would have been years. That means that there is no field The science has changed enor- unthinkable 10 years ago, and yet now that is having an easy time. mously. In 1993, the genome project can be done by a relatively small group was just getting started. There were of dedicated and computationally great concerns about NIH getting sophisticated researchers. Both the U.S. House and into “big science,” where teams would Technology has opened up those Senate have proposed be brought together to work on large doors to us. We can push much faster projects. Technology was seen as not and further than I thought possible increases to the NIH quite as elegant as other kinds of fun- in my lifetime to understand how a budget in the upcoming damental bench research. Nowadays, genome, a cell, a tissue and an organ- we see technology as such a powerful ism works. Trainees just getting into budget. Isn’t that right? driver. research can’t imagine how we ever That’s right, and we’re thrilled to Certainly, you can’t look at the learned anything without the ability see this kind of strong bipartisan sup- biomedical literature without real- to ask such comprehensive questions. port to help turn around the 12-year izing that the number of articles that They look at what we were able to slide in our resources. Both the House have multiple authors has grown do 20 years ago and say, “Surely you and Senate appropriations subcom- substantially over 22 years. That is an didn’t stop there!” Well, we had to. mittees have voted for a significant indication of the way in which science But now look where we are. (budget) increase for NIH. That, I is now much more of a team effort. Rajendrani Mukhopadhyay think, deserves cheering. Some of the most rewarding experi- ([email protected]) is ences scientists are having now come the chief science correspondent You’ve been at the NIH from being part of interdisciplinary for the American Society for Bio- teams that bring skills from multiple chemistry and Molecular Biology. Follow her on Twitter at twitter.com/rajmukhop. since 1993. How have perspectives to the same problem.

OCTOBER 2015 ASBMB TODAY 35 ANNUAL MEETING

PLENARY LECTURER ‘Trust your own imagination’ By Rajendrani Mukhopadhyay

Success in science comes when you stick with interest in science in the what you personally find most interesting, says first place? Anna Marie Pyle. And she does as she says. Pyle, a faculty member at Yale University I grew up surrounded by people and a Howard Hughes Medical Institute investi- who were interested in science in gator, has stuck with her fascination with RNA Albuquerque, N.M.. We did a lot since she was a graduate student. During her playing around with rocks and miner- graduate work with Jacqueline Barton, then at als. We would go hiking. We also had Columbia University, Pyle worked on DNA but elaborate chemistry sets, and we’d became intrigued by ribozymes. To dive into the play with prisms. I was surrounded RNA world, Pyle took up a postdoctoral stint by a scientific mindset. To me, one of with Thomas Cech at the University of Colorado the things that is exciting about life and then formed her own group focused on the is that physics and chemistry pervade structure and function of large RNA molecules and RNA-remodeling enzymes. everything. These days, members of the Pyle laboratory use biochemical, biophysical and But I didn’t commit to a scientific computational techniques to understand the structures and functions of large career early on. I went to a liberal arts RNA molecules and the enzymes that act upon them, such as RNA helicase institution – to Princeton (Uni- enzymes and other RNA-stimulated ATPases that work as translocases, RNA versity). I studied a lot of different remodeling enzymes, folding cofactors, and signaling enzymes. things, including public policy and Slavic languages. It wasn’t until very late in the game that I decided that I How did you become About half of the lab works on was going to get a Ph.D. in chemistry. large, highly structured RNA mol- interested in working ecules. Some are catalytic, and some Were your parents with RNA? are epigenetic control elements. The other half of the lab works on a very scientists? When I was a graduate student, I specialized class of motor proteins My dad was a cardiologist and was working on designing small mol- that are RNA-stimulat ed ATPases. a medical researcher. He also was ecules that would recognize sequences They are important for remodeling involved in the space program and the and features of double-stranded DNA. RNA and some of them function as military. But he was also a chemistry Around that time, the discovery of RNA-activated signaling enzymes. undergraduate, and he envied me ribozymes was made. I got really They all belong to the same phyloge- going to graduate school instead of excited about the potential for elabo- netically conserved family. medical school! He got to enjoy it rate structure in RNA. So I decided vicariously through me. that if I was interested in molecular Although most of the lab does recognition by nucleic acids, I should experimental work, we do have a big probably work on RNA. That’s when computational contingent. We do a You mention your training lot of development of new programs I contacted Tom Cech about working for modeling, analyzing and predict- in public policy and in his lab. I’ve been working on RNA ing RNA structures. We’ve had to languages. Do you think ever since. develop tools to enable us to better solve structures. that’s been important to What does your lab you as a scientist? focus on? What triggered your It has. All of the education that

36 ASBMB TODAY OCTOBER 2015 PHOTOS COURTESY OF ANNA MARIE PYLE Pyle with her daughters. I was fortunate enough to receive biological roles. Beginning to get a give is that you want to pick problems helped with my writing and com- good intellectual handle on what all that you’re really passionate about. munication skills. The fact that I of these different noncoding RNAs It should make you happy to know was required to take a lot of history, actually are doing mechanistically is a that you’re going into lab that day to language and literature has been a tre- huge challenge. A parallel challenge work on that problem. That’s a very mendous asset. I sometimes think that is to organize and draw mechanis- personal thing. There’s always a lot of the time my favorite history professor, tic conclusions from the wealth of pressure to work on what other people Dr. Arno Mayer, spent teaching me bioinformatic data that is emerging on think is interesting. I think you have how to write a good paper was one noncoding RNAs. Another challenge to reach inside yourself and deter- of the most educationally important is how to organize the mechanistic and mine what you find interesting. The times in my life! structural information that is accumu- rest really does follow if you’re doing I suspected that one of the best lating about RNA and RNA-binding something that makes you happy and ways to get involved in science policy proteins and leverage (the informa- is really exciting to you. was to become a strong scientist. That tion) for small-molecule inhibitor But I can’t underscore enough how has turned out to be true. I decided and activator design. It’s a big frontier personal that is. Students are con- that if I cared about science policy, I out there. A lot of these molecules are stantly buffeted by trends. You really should get out there and understand really interesting targets. It also would should decide what you personally how to do good science and make an be great to bring together people find is interesting. In the beginning, impact scientifically. who are trained classically in rigorous other people may not see it the same enzymology with projects that involve way as you. But as my grad school What do you think are fascinating new enzyme families, advisor, Jackie Barton, used to tell me such as those involved in epigenetic repeatedly, trust your own imagina- some of the big challenges phenomena and signaling. tion to know why something is really in your area of research? significant and why you want to It’s become clear that we transcribe What advice would you give explore it. many large, functional RNA mol- Rajendrani Mukhopadhyay ecules that do not encode proteins. young scientists wanting to ([email protected]) is But we know very little about what be successful the chief science correspondent they are doing. We have few pheno- for the American Society for Bio- in research? chemistry and Molecular Biology. types and functional readouts of their Follow her on Twitter at twitter.com/rajmukhop. The advice that I most frequently

OCTOBER 2015 ASBMB TODAY 37 ANNUAL MEETING

PLENARY LECTURER Sliding into biology By Rajendrani Mukhopadhyay

thinking about big proteins. They How is the cell’s interior organized? That is were thinking about making polyester the question that has interested Michael Rosen for the war effort back in World War at the University of Texas Southwestern Medical II. They figured out that polymers will Center since he started out as an independent phase separate. They will become like researcher. These days, the Howard Hughes oil-and-water mixtures. Medical Institute investigator, who trained as a Sure enough, that is the way our chemist and chemical engineer, has been focusing system behaves. The WASP protein on the analysis of cellular compartments that are and its ligand, NCK, when mixed not bound by membranes. together in sufficient concentration, phase separate. You get these little droplets that float around in the aque- ous solution. The connection that we made was that perhaps this could be a How did you become and somewhere around nine bind- mechanism to organize the cytoplasm ing sites for the SH3 domains in the and the nucleoplasm of cells. interested in cell WASP protein. We pretty quickly real- There are many different cellular organization? ized that was going to be a biochemi- compartments that are not bound by cal mess. membranes. Most of the organelles In 1996, I started my lab at the A lot of the work that we do in the people think about – the nucleus, (Memorial) Sloan Kettering Cancer lab is with (nuclear magnetic reso- mitochondria and lysosomes – are Center, just a few years after Alan nance spectroscopy) and (X-ray) crys- membrane-bound compartments. But Hall’s lab published seminal observa- tallography. You can’t deal very well there are also a whole bunch of much tions reporting that the Rho family with mixtures in NMR and definitely GTPases control the actin cytoskel- less well-understood compartments not with crystallography. It was a eton. I thought that would be a great that are not bound by membranes. really confusing problem for us. But it thing to start my lab in. Maybe the mechanisms that we’re was an important one, and we needed But my interest has shifted over studying in vitro also can account for to figure out how to solve it. time from the signaling molecules these cellular structures. I got very lucky. I had two terrific to the actin cytoskeleton itself. We students, Pilong Li and Hui-Chun were studying a very important actin Cheng, who went away one summer It’s interesting you’re regulatory protein called WASP, the to the quantitative biology course Wiskott-Aldrich syndrome protein. borrowing ideas from that’s taught at Los Alamos National We hit on a molecular interaction (Laboratory). They heard a seminar chemistry. How does that was very confusing. This was five there where people were trying to crossing two different years ago. The WASP protein has a use ideas from polymer chemistry to large, disordered loop and a string of areas influence your understand multivalent proteins and binding sites for what are called SH3 their multivalent ligands. It turns ideas? domains. It turned out that one of out it’s an old problem in the field of the important ligands of WASP has I have a dual (undergraduate) polymer chemistry that was solved in multiple SH3 domains. We started to degree from the University of Michi- the early 1940s. think about what kind of complexes gan. One’s in chemistry, and one’s in The polymer world has told us how this kind of a system was going to chemical engineering. It’s been a slide molecules like these should behave, make. You’ve got three SH3 domains toward biology since then. Chemistry although the polymer scientists weren’t gives me a strong quantitative foot-

38 ASBMB TODAY OCTOBER 2015 ing. I want to understand biological processes in quantitative terms as I want to understand biological processes in much as I can. I think the engineering quantitative terms. helps in that a lot of engineering is developing mathematical models that describe various phenomena. Kay and Tony Pawson. Lewis came The way you phrase that implies from Ad Bax’s lab. (Authors’ note: Ad that there was a time when I was not Bax is well-known for his development interested in science! I was the kid How did the slide into of NMR methods and their applica- who, at the earliest age, memorized biology happen? tions to biology.) Tony discovered the the names of dinosaurs. I was the I did my Ph.D. with Stuart Sch- SH2 domain and recognized that it kid who loved running around at reiber. I joined Stuart’s lab the year bound phosphotyrosine. I was lucky the beach and looking for stuff in that he moved from Yale (University) to do a joint postdoctoral appoint- the sand. I remember wanting to be to Harvard (University). Stuart was a ment between those two labs who a mathematician and have always hardcore synthetic organic chemist at were already collaborating (at the enjoyed math. That kind of morphed Yale but always had been interested in University of) Toronto. sometime in high school into science applying chemistry to biological prob- and engineering. lems. When he moved to Harvard, What would you say are the he allowed his interests to manifest in big, challenging questions Do you have any hobbies? his research program. I was teamed I really love science. Much of the up with a postdoctoral fellow from in cellular organization? time, if you ask me, “Hey, Mike, Martin Karplus’ lab to solve the struc- I certainly think membrane- what are you thinking about?” it’s ture of the FK506 binding protein as independent compartmentalization is something to do with science. I’m not my thesis project. A lot of the lab was a very interesting and very important entirely one-dimensional, though. My doing synthetic chemistry. I was the idea. How do these structures form, wife and I love to cook and eat. We oddball doing structural biology using and what do they do? How does also like to travel a fair bit. I didn’t NMR, the same tool as the chem- the mitotic spindle get together? Or know early on, but you get to travel as ists but in a different way, applying it the microtubule-organizing center? a scientist. There are very good profes- toward the structure of a protein. Or clusters of membrane receptors? sional reasons to be in different places I became interested, along with a There’s got to be some way of organiz- of the world. While you’re there, you lot of people In Stuart’s lab, in signal ing these things. Why should cells go meet people, taste the food, do a little transduction at that point. It was the to the trouble of creating any of these bit of sightseeing. It’s a really nice side rise of the signaling era right as I was other structures? It’s not clear why benefit. finishing my Ph.D. As a postdoc, I concentrating molecules together like realized that I needed to strengthen that should be useful to biology. Rajendrani Mukhopadhyay my skills and knowledge in NMR ([email protected]) is the chief science correspondent spectroscopy, and I also needed to What drew you into for the American Society for Bio- learn biology. chemistry and Molecular Biology. I did a joint postdoc with Lewis science? Follow her on Twitter at twitter.com/rajmukhop.

OCTOBER 2015 ASBMB TODAY 39 ANNUAL MEETING

PLENARY LECTURER Mad about metabolism By Rajendrani Mukhopadhyay

become convinced that metabolism Jared Rutter at the University of Utah got is much more active in determining hooked on cell metabolism early in his career. what the cell does rather than just His laboratory focuses on understanding the doing what it’s told. dynamic nature of cell metabolism. As Rutter points out, cell metabolism typically is viewed as Who drew you a passive process. But as his laboratory and others are finding out, there is more to it than simply into science? churning out molecules of ATP. I have an uncle who is a promi- Earlier this year, Rutter was selected by the nent scientist. (Author’s note: Rutter’s Howard Hughes Medical Institute to be one of uncle is William Rutter, formerly its newest investigators. He was also one of the at the University of California, San 10 finalists in the life sciences category this year Francisco, and now at Synergenics.) for the Blavatnik Awards for Young Scientists. In addition, he is a member of His influence encouraged me to think the American Society for Biochemistry and Molecular Biology Council. about science. I fell in love with it when I started taking the classes and doing a little bit of research as an I know your lab works and stem cells. undergraduate. on cellular metabolic We have a couple of other projects I went to (the University of Texas- that are focused around mitochondrial Southwestern at Dallas) as a graduate homeostasis. Can you quality control. What happens when student. I had a really great experience tell me in a little more mitochondria become aberrant or there. It encouraged me to pursue a damaged? How does a cell respond research career in academia. I stayed detail about the ongoing to that to repair the damage or adapt and did a postdoc for about a year and projects? to it? a half. Then I took a job in Utah, and Another segment of the lab is I’ve been here ever since. (Author’s The overarching question that my working on kinase signaling. A spe- lab tries to address is how do cells note: After completing his Ph.D. with cific kinase we’ve worked on for some Steve McKnight at UT-Southwestern, adapt their metabolism to be opti- time called PASK integrates metabolic mally suited for the behaviors that the ASBMB’s current president, information and signals to control Rutter continued his training there they are engaged in. A complementary the behavior of cells in different ways, part of that is when cells are forced through the Sara and Frank McK- including how cells use their available night Fellowship.) to change their metabolism through energy. mutations or through a change in the What are some environment, how does that cause How did you develop an them to change their behavior or fate? of the big questions Those are the two interlinked ques- interest in metabolism? in your own field? tions on which my lab is focusing. It came pretty early on in my sci- We have a number of different entific career. I’ve become convinced One of the biggest challenges in projects focused on understanding that the metabolic situation of the cell our field is the metabolic heteroge- basic mitochondrial functions and is a really important environmental neity of cells. When we grind up a how that relates to cellular decisions. factor that, until recently, was largely liver, for example, and measure some One project is aimed at understanding overlooked as anything other than parameters, we make an implicit how changing mitochondrial oxida- just providing ATP and enabling the assumption that we’re measuring tive metabolism influences cancer cells cell to go about and do its job. I have 10 million cells that are roughly the

40 ASBMB TODAY OCTOBER 2015 and cell B will take up the lactate and oxidize it to make CO2. There are sev- eral similar situations, and it is critical for us to understand them. Are there any tools that let you piece this together at the single-cell level? Not in a simple way. That’s some- thing that my lab is hoping to do in the future. There are tools for studying individual cells, but they rarely have been applied to the study of metabo- lism. What are your hobbies? I have four children. My wife and I spend most of our time managing them when I’m not in the lab! I like to play golf. Outside of my family and my work, that’s probably the hobby that I enjoy the most. I try to do that whenever I can, especially when I travel. I plan to play golf in San Diego when I’m there for the ASBMB annual meeting! Also, I like to ski. I live in Utah, which is a great place for skiing and other outdoor activities like biking and hiking, which I also enjoy. What words of advice would you give to scientists in training? A phrase I heard recently was “the deletion test.” When we evaluate our contributions to science, we should think about the deletion test: If we weren’t there, would the progress of the scientific community be any differ- ent? I think the best way to pass the PHOTO COURTESY OF JARED RUTTER deletion test is to be working in areas Rutter on the green. and using technologies that other same. In reality, the 10 million cells single-cell level and get at the meta- people aren’t. That way, we’re breaking are different, and our measurements bolic heterogeneity of a population of new ground. typically average over those 10 million cells, whether it’s in a tissue, a tumor cells. The result is we get a pretty low- or a dish. These cells aren’t acting in Rajendrani Mukhopadhyay ([email protected]) is resolution view of whatever parameter isolation but are actually communicat- the chief science correspondent we’re studying. ing metabolically. For example, there for the American Society for Bio- One of the areas that I think is very are a number of situations where cell chemistry and Molecular Biology. interesting is to study metabolism at a A will take in glucose and make lactate Follow her on Twitter at twitter.com/rajmukhop.

OCTOBER 2015 ASBMB TODAY 41 ANNUAL MEETING

PLENARY LECTURER An explorer of cells By Rajendrani Mukhopadhyay

driven research where the applica- The unfolded protein response is one of the tions aren’t apparent at the onset. It cell’s quality-control systems. The response helps has been a major struggle with the cells decide when to fix proteins and when to (National Institutes of Health) – hav- commit suicide. The laboratory of Peter Walter at ing to justify translational implica- the University of California, San Francisco, has tions at the onset rather than letting been at the forefront of identifying the machin- scientists be explorers and recognizing ery and mechanisms that oversee protein synthe- the incredible value of accumulating sis, folding and targeting as well as the signaling knowledge for knowledge’s sake. relays that allow organelles to communicate with each other. As the unfolded protein response makes life-and-death decisions for the cell, it has You are also the co-author been implicated in numerous different diseases, of “Molecular Biology of including some inheritable forms of protein- folding diseases, neurodegeneration, diabetes and cancer. the Cell.” How has the Walter got into studying protein targeting as a graduate student. He was textbook influenced you? working in the laboratory of Günter Blobel at The Rockefeller University when As authors of this book, we read he discovered the signal recognition particle that guides proteins to where they every chapter. We are all intimately need to be. Later, in his own lab at UCSF, he initiated work on the unfolded involved with every part of it. (The protein response, initially using genetic approaches in yeast. book) has made me a much better In a recent New York Times profile, Walter described how his time in the scientist by expanding the scope of Blobel laboratory began serendipitously. He was an exchange student at Vander- my knowledge base and staying at the bilt University, visiting the U.S. from Germany, and decided to apply for a forefront of what is exciting in numer- Ph.D. program at Rockefeller. He was put on a waiting list. At the last minute, ous different fields. a student decided to decline the invitation to join the program, giving Walter a spot. Ever since that time, Walter who is also a Howard Hughes Medical Institute investigator, has been focused on learning how cells check that all the What are the other fields proteins and organelles are functioning properly. outside of your expertise that you find exciting? whether we can modulate the basic What are some of the The technology that we have at cellular mechanisms to find some our fingertips is just tremendous current projects going on therapeutic window in which we may these days. For example, there’s the be able to do some good in disease. in your lab? What has you CRISPR technology. We can now In this sense, we’re trying to build do incredibly sophisticated genetic excited? bridges between the basic science experiments and get deep insights into We have been studying the discoveries and clinical applications. unfolded protein response for many even the most complicated regulatory years. I trained initially as a chemist, What are some the big events. It’s a real revolution in having so we have a very strong mechanis- the tools to engineer mutations in tic angle to understanding how the challenges that you see in mammalian cells. Basically, mamma- machinery of the cell works to iden- research? lian cells are now becoming as acces- tify the folding status, communicate it To convince the public and the sible as yeast used to be 30 years ago. into constructive corrective measures and, if that doesn’t work, make a deci- funding agencies that there is an sion to kill the cell. We’re exploring incredible value in basic, curiosity- In the New York Times

42 ASBMB TODAY OCTOBER 2015 come to the lab and don’t have fun, Proteins are not magic beings. They are complicated they should reconsider their careers. They might as well go out and make chemicals, and they obey the laws of thermodynamics. money. What are your interests profile, it mentioned your wonderful time. Again, he gave us freedom to explore things of our own. outside of the lab? parents owned a chemist’s And at Rockefeller, my Ph.D. adviser, I do a lot of art: sculpture, wood- shop in Berlin, Germany. Günter Blobel, was an incredible men- working and welding. These days I What are some of your tor and shaped my career in so many don’t do experiments with my own ways. hands, and just sitting all day in front favorite memories of the of a computer is not as rewarding as it shop? You straddle the worlds is to do things manually. I’ll get that kind of satisfaction from my base- It gave me the opportunity to of chemistry and biology. ment projects. Currently, I’m building appreciate the wonders of chemistry. I Is there something to be a fountain for the garden, which I’m started as a young boy playing around welding from copper. It’s been going with chemicals, very much in the said for being trained in on for a long time. pyrotechnical angle! It was incred- one field and working in ibly inspiring to me—the conversion of matter and the nice sparks and another? Are there any words of explosions one can so easily create. I always felt that thinking chemi- advice you wish you were (My experiments) became a little cally has been an advantage in my more sophisticated as I grew older and career. Proteins are not magic beings. given when you were started studying chemistry. I found They are complicated chemicals, and younger? chemistry, personally, a little bit too they obey the laws of thermodynam- I’ve always been surrounded by constricting, and the questions in ics. It puts a more reductionist angle spectacular mentors and worked in biology much bigger. I evolved into on the questions we ask. I never feel great communities and been given what I am today, an explorer of how that there are limits to our under- many words of advice. And many cells are built and function. standing. And I think that comes with things you can only learn by first our appreciation for chemistry. failing. Overall, I’ve no regrets. Many Who has been important in things happened that were unex- shaping you as a scientist? What characteristics are in pected, but I think if I had been more a good scientist? aware of how challenging it can be to I had a fantastic chemistry teacher carry on in this job, I might have just in high school. He was really inspiring Boundless curiosity. Not being been discouraged. So, in a way, I got and gave us a lot of leeway of play- discouraged by the many failures that to live in my dreams. ing in the back rooms. In fact, I had come with scientific pursuit and all of the bureaucracy that nowadays comes fantastic mentors all the way through Rajendrani Mukhopadhyay my career. When I first came to this with our jobs. A lot of tenacity for ([email protected]) is sticking with it. country, I spent a year in Nashville. the chief science correspondent For me, science really is an adven- for the American Society for Bio- My host was an organic chemistry ture. It’s not a 9-to-5 job. And it never chemistry and Molecular Biology. Follow her on Twitter at twitter.com/rajmukhop. professor, Tom Harris, and it was a will be. I tell my students that if they

OCTOBER 2015 ASBMB TODAY 43 ANNUAL MEETING

PLENARY LECTURER Taking optical microscopy by STORM By Rajendrani Mukhopadhyay

the real-time process. If you only get Xiaowei Zhuang at Harvard University is one five frames, you get a very choppy of the pioneers in the field of super-resolution movie. With super-resolution imag- microscopy, which overcomes the problem of ing, whichever method you use, the the diffraction limit in optical microscopy. First number of frames one can get often is described in 1873 by one of the founders of limited. optics, Ernst Abbe, the diffraction limit prevents I can tell you about some of our researchers from using light to distinguish two applications. One area is in neurosci- objects that are apart by 200 nanometers or less. ence. We discovered a membrane The field of super-resolution microscopy was skeleton structure in the neuron using recognized by the 2014 Nobel prize in chemistry. STORM. It’s a beautiful structure In 2006, Zhuang’s team was among the first in the axons. We saw these highly to describe a method to overcome the diffrac- ordered periodic rings of actin that tion limit. The method is called stochastic optical are connected by spectrin tetramers. reconstruction microscopy, better known as STORM. This structure is important for the In STORM, a weak ray of light is used to stochastically turn on a small mechanical properties and func- subset of photoswitchable probes. After the first subset of probes is imaged and tions of axons. And it anchors many localized, it is turned off. Then a different subset of probes is turned on, imaged important membrane molecules and and turned off. The process is repeated thousands to tens of thousands of times. enzymes, so there might be func- The final high-resolution image is a reconstruction of molecular positions deter- tions in addition to (the) mechanical mined from the thousands of collected images. functions. Mutations in some of its Zhuang, a Howard Hughes Medical Institute investigator, and her team are molecular components are found in pushing the boundaries of super-resolution microscopy and applying it to bio- diseases, so we’re also studying its logical problems. The group is also working on transcriptome imaging based on disease relevance. single-molecule fluorescence microscopy. (Another area is) how DNA is What’s the cutting edge meter resolution, then you (could) structured in the nucleus. We know open up another new window. That’s a huge amount of one-dimensional with STORM? not incremental. It would allow you information of the DNA, such as the In terms of technology develop- to study a lot of important problems DNA sequence, the modification pro- ment, there are a number of things that we still cannot do with super- file and the protein-binding profile of that are very important. One still is resolution imaging. the chromatin. But there is accumu- the spatial resolution. The first-gener- There’s also the dynamics side. lating evidence that the three-dimen- ation work of STORM got resolution There, two aspects are important: the sional structure of chromatin and the time resolution and the amount of that’s 10 times better the diffraction- dynamics (of the structure) are also limited resolution. That 10-times- dynamic information. The simplest way to understand the second aspect very important for the regulation of better resolution allows you to see a gene expression, replication and other is if you have (to think about) a lot more inside biological specimens functions. We’re using STORM to movie. A continuous movie of 100 than we could see before. But if you learn what the 3-D structure of chro- could get to approximately 1-nano- frames can give a very good idea of matin and chromosome is like.

44 ASBMB TODAY OCTOBER 2015 What are you doing with sudden, possible. However, I must say that transcriptome imaging? this is an overly simplified The goal is to get the spatially picture, because identifica- resolved transcriptome of individual tion of each bit has an error; cells. For many different types of cells, accumulating errors from 16 RNAs are not uniformly distributed. rounds of imaging is severe. The local distribution of transcripts We solved the problem by is important for the building and using encoding schemes that maintenance of local structure. Dif- can detect and correct errors. ferent types of cells have different gene-expression profiles, and that is How did you important for cell fates, behaviors and functions. become interested There are about 60,000 different in microscopy? coding and noncoding RNAs (in a My Ph.D. thesis was on human cell). For each RNA, I could nonlinear optics, which is have oligo probes, each attached to a spectroscopy approach. different colored fluorophores. If I It had nothing to do with (were to) have 60,000 colors and if biology, but it gave me a I could distinguish 60,000 colors strong training in optics. My simultaneously, I would be able to do supervisor was one of the transcriptome imaging. Obviously pioneers in nonlinear optics, that’s not possible. Ron Shen (at University of PHOTO COURTESY OF FREDFIELD.COM The other extreme is to use one California, Berkeley). I used Zhuang’s lab developed the optical technique called STORM. color but image one RNA species at a it as a tool to study liquid at physics when I was little, because time by flowing in (complementary) crystals, polymers and so on. my dad told me that I had very good oligos (one set at a time). I can do it My first microscopy experience was physics intuition. I always liked 60,000 times, provided that I have when I was a postdoc at Steven Chu’s physics. Even into college, I did not enough students and postdocs with lab at Stanford. (Author’s note: Chu quite like biology and did not think enough patience and the cell is not is a former secretary of energy for the it was as elegant (as physics). Now I damaged during that process! That’s Obama administration.) My work was really love biology. The fact that there equally unfeasible. looking at how RNAs folded. It was are so many unknowns makes it an I came up with an idea that doesn’t purified RNA molecules scattered on extremely fascinating area to study. require 60,000 fluorophores and coverslips, and I inferred the confor- doesn’t require 60,000 rounds of mation of RNA using a spectroscopy What advice would you imaging: Image a combination of approach called FRET. I began to RNAs in each round but different image biological specimens and study give to graduate students? combinations in different rounds. For biomolecules without taking them out Be fearless. Also, it’s important to example, we can encode RNAs with of the cell when I started my indepen- be very strongly motivated and willing a binary code. Each RNA is associ- dent faculty position at Harvard. to spend a lot of effort. Try not to get ated with a code of 11011 and so tunnel vision, but be open-minded on. In the first round, we only image to broadly learning about all kinds those RNAs (whose) binary codes What sparked your of new scientific frontiers. Good sur- read 1 in their first digit. Then we interest in science? prises await if you have an open mind, quench those fluorophores and image Probably family influence, because are fearless and are persistent when a second set of RNAs whose binary both of my parents are professors at you encounter difficulties. codes read 1 in their second digit. In the University of Science and Technol- order to distinguish 60,000 different ogy in China. I’ve always wanted to Rajendrani Mukhopadhyay binary codes, I only need 16 rounds be a professor – even before I knew ([email protected]) is of imaging, because two to the 16th the chief science correspondent exactly what a professor was! I never for the American Society for Bio- power is greater than 60,000. It makes changed my mind. chemistry and Molecular Biology. something almost impossible, all of a I knew that I was probably good Follow her on Twitter at twitter.com/rajmukhop.

OCTOBER 2015 ASBMB TODAY 45 CAREER INSIGHTS The courage to find myself By Suzanne Barbour

’ve only recently developed a five- year career plan. It took nearly I half a century of my life and two decades in academia, but I finally found my professional calling. Like a lot of people, my first career goal was medicine, largely because I was interested in the life sciences and did not know what else a biologist could do. Two realizations changed my path. They both came during high school when I had the chance to be a candy striper at a local hospital. I learned two very important things. One was that it takes a very special kind of person to deliver health care to a patient in a compassionate man- ner. The other was that I am not that kind of person. PHOTO COURTESY OF SUZANNE BARBOUR I was very fortunate to be recruited into a biochemistry research labora- sions and journal clubs; and, most a fundamental scientific principle that tory during my first undergraduate importantly, one-on-one interac- would lead someone else to a cure. semester at Cook College (now the tions in my research laboratory at the These were sobering thoughts for Rutgers School of Environmental and Virginia Commonwealth University. someone who had defined herself as a Biological Sciences). Through that I supervised students on projects research scientist for more than half of experience, I got hooked on research, related to my major area of interest, her adult life. and I never looked back. There was phospholipases and phospholipid And then came another eye-opener never a question about whether I metabolism. Over the years, my sci- of my career: I realized that I might would go to graduate school, only ence came to define me: When asked not be the one who cured the disease which institution I would attend. who I was, I typically answered with or uncovered the principle but could I only realized that education and “research scientist” or “lipid biochem- be involved in training the person research training would play impor- ist.” I was also a member of nearly who did. After 20 years in academia, tant roles in my career when I was 100 graduate-student advisory com- I finally realized that I wanted to be given responsibility for training an mittees and, eventually, a director of a dean of a graduate school. undergraduate student one summer graduate program in biochemistry. I had directed a graduate pro- during my Ph.D. training at Johns Through those experiences, I gram, served on training-grant study Hopkins University. Although the learned that I had a knack for gradu- sections at the National Institutes of experience was not 100 percent suc- ate education and a gift for connect- Health and done strategic planning cessful (the student forgot to dilute ing with students. I got a lot of through my role as the director of TAE buffer and boiled an agarose satisfaction from watching more lights research training in the VCU Center gel), I realized how much satisfaction turn on in the eyes of my colleagues’ on Health Disparities. But I real- I derived from seeing the light turn students. ized that I lacked the leadership and on in a student’s eyes. I also began to realize that my budgeting skills necessary to aspire to I spent the next two decades individual research program was a deanship. This was the genesis of my turning that light on through formal dying. I would never cure a metabolic five-year plan. platform lectures; small group discus- disease and likely would not uncover Becoming a program director at

46 ASBMB TODAY OCTOBER 2015 the National Science Foundation needed but also to learn tough lessons first UGA oral exam was in October). offered the opportunity to broaden about myself: I don’t handle change At my core, I am still a lipid bio- my knowledge of the biological sci- well and have a somewhat unproduc- chemist, a scientist and a researcher. ences and, at the same time, develop tive need to be in control. But now I have added responsibilities the leadership, budgeting and other My collective experiences will serve that will permit me to watch the light administrative skills that I needed to me well in my new position as the come on in the eyes of students in aspire to be dean of a graduate school. dean of the graduate school at the music, history, forestry and other dis- Although I knew this, I hesitated University of Georgia. Although I ciplines that are completely unrelated when I was offered the position at the still miss working in the laboratory, I to mine. NSF. It meant leaving my comfort can keep up with my science through Not bad for someone who took zone, admitting that my research collaborations (we published a paper nearly five decades to develop a five- program was finished and redefin- in the Journal of Biological Chemis- year plan. ing myself as something other than a try and submitted a grant proposal Suzanne Barbour is at the University research scientist. It meant checking last spring), by attending seminars of Georgia as the dean of the graduate my ego and finding the courage to (I have a faculty appointment in the school. She can be reached at look at myself in a different way. My biochemistry and molecular biology [email protected]. 18-month stint at the NSF not only department at UGA), and by serving allowed me to develop the skills I on graduate advisory committees (my

OCTOBER 2015 ASBMB TODAY 47 EDUCATION Six things your mentor wants you to know (but probably won’t think to tell you) B y P. H. Grey

ost mentors do a solid job If I don’t hang out and chat project on the back burner for a informing a new undergrad at the lab, it doesn’t mean short time to make time for my other M of the basic requirements of a 1. that I don’t like you. It prob- priorities. research position. Typically, they cover ably means that I’m overextended I hope that you’ll be inspired the expected time commitment, lab or don’t have much spare time each by your research project, but safety procedures, lab dress code, and day. I might be in the lab more hours 3. if you’re uninterested or would guidelines for writing a pre-proposal per day than you are in an entire rather be anywhere else than the lab, or end-of-semester report. When it week, and I still might not have you’re not going to get much out of comes to working at the bench, most enough time to accomplish my goals. your research experience. If you don’t mentors remember to share techni- Alternatively, your lab schedule might show up regularly or don’t work hard, cal tricks with a new researcher and overlap with my busiest time of the I won’t go out of my way to tell the offer guidance on getting organized, day, or I might need to leave lab at professor you’re underperforming, programming equipment and finding a specific time each day, leaving me but I’ll be honest when she asks for research supplies. no extra time to socialize. Therefore, my opinion. So if you’re not excited But sometimes, because we have I might focus on conversations that about the project or what I have to teach you how to interpret results teach you, it would be better for you been in science for a long time or or gain a new research skill, because to make a professional exit and find because we are distracted by our own I want our limited time together to a research project that inspires you. research goals, we forget what it was make the greatest impact on your I’ll understand, because I know that like to be a new undergrad adjusting research experience. That might my area of research isn’t right for to a professional lab environment. mean sticking to conversations about everyone. However, if you show me We don’t remember the nervousness research and science. that you value the time you spend or anxiety that often accompanies Just as starting a new research in the lab, I’ll be happy to teach you the unknown. We don’t remember position is tiring for you, everything you need to succeed – and what it was like to try to understand 2. working with a new undergrad you’ll earn an epic letter of recom- and fit into the lab’s culture. We is challenging for me. And sometimes mendation. don’t remember how mysterious our I need a break just like you do. On If I say “thank you” more research mentor first seemed or the occasion, I might send you home often than “good job,” it’s early, might not have something for because I appreciate your uncertainty we felt when he appeared 4. you to do, or might not be immedi- efforts, but there isn’t much praise to change our experimental plans ately responsive to your email or text. given in a professional research lab randomly from time to time. Conse- It doesn’t mean I don’t like you (see for meeting basic expectations. You’ll quently, it might not occur to us to No. 1), but I might need to restruc- realize quickly that it wouldn’t mean address these things. ture my time temporarily, or I might much if I praised you for learn- To help ease your transition into need a break from researchlike things. ing how to pipette or prepare a 5M your new lab, here are six things that Although it might be difficult to sodium chloride solution. I’ll prob- your research mentor probably wants believe, I do try to have some type of ably save the praise for things such as you to know, even if she doesn’t think life outside the lab. This means that I when you master a difficult tech- to tell you. might need to put a new undergrad’s nique, come up with a good trouble-

48 ASBMB TODAY OCTOBER 2015 shooting idea, or stay late to help sional development and will help times as well (sometimes until I’m someone else finish an experiment. you to make a deeper connection to asked to move on to another subject). I want you to feel proud of your your research project. So I hope you It’s impossible not to be proud after accomplishments, and I know that remember that I’m not being a jerk you present your first poster or give a false praise won’t help you do that. and it’s not a power thing when I ask polished talk at a lab meeting. Watch- When I don’t immediately you to try to answer your own ques- ing your CV and self-confidence give you the answer to your tion – it’s a mentoring thing. grow is one of the best parts of being 5. question and instead coach Sometimes I brag about how a mentor. Bragging about it is pretty you through the answer, it’s because awesome you are to my col- good too. I’m investing in you. Trust me – even 6. leagues. When I do, I probably if I have mentored 50 other under- just call you “my undergrad,” but if grads, it takes more effort on my you’re working hard and investing P. H. Grey ([email protected]) works part to ask you to explain, analyze or in your research experience, I’ll be as a molecular biologist and is co-creator of Undergrad in the Lab reason through your own question excited to share how much fun it is (undergradinthelab.com). She is than simply to give you the answer. to mentor a student who is genuinely co-author of the new book But I know that coaching is critical to enthusiastic about science. And I’ll “Getting In: The Insider’s Guide to Finding the both your personal and your profes- probably make my spouse listen a few Perfect Undergraduate Research Experience.”

OCTOBER 2015 ASBMB TODAY 49 EDUCATION Action plans and best practices for undergraduate education By Ben Caldwell, Mary Huff and Quinn Vega

olecular biology and biochem- were fully engaged, and that is what students for careers in industry and istry educators with a wide made this meeting a success! They the health professions and highlighted M variety of viewpoints on best created a pulse of excitement that academic and soft skill sets students practices for undergraduate educa- reflected the passion we all share for need for successful careers in the tion, gathered for the American Soci- undergraduate education.” sciences. Cheryl Bailey, the dean of ety for Biochemistry and Molecular Action plans were a key element of natural and health sciences at Mount Biology-sponsored special symposium the three-day conference. Group ses- Mary University and a former pro- “Transforming undergraduate educa- sions provided time for participants gram director at the Howard Hughes tion in the molecular life sciences.” to develop individualized teaching Medical Institute, delivered a keynote The fourth in a biennial conference plans that incorporated strategies and on critical issues for preparing series that began in 2009, the July 30 activities from the meeting. Partici- students for biomedical and STEM to August 2 conference took place at pants also were encouraged to expand careers. Missouri Western State University in their support networks by identifying Methods to promote deeper learn- St. Joseph, Mo. Attendees included others who could provide them with ing were the focus of a talk by Ellis faculty representing a range of institu- advice and expertise. Bell of the University of San Diego, tions, graduate students, postdocs, The conference opened with talks who described the latest results of the administrators and industry from Jennifer Fretland of Takeda ASBMB’s National Science Founda- representatives. Pharmaceutical Company Limited tion grant, in which workshops across Mary Huff, one of the conference and Bruce Horazdvosky of the Mayo the U.S. were used both to identify organizers, said, “The participants Clinic, who spoke about preparing core biochemistry and molecular biology concepts and to develop assessment tools for undergraduate educa- tors. Jenny Loertscher of Seattle University presented on how stu- dents’ understanding of threshold concepts can help prepare them for upper-level BMB content, and Martina Rosenberg of the University of New Mexico discussed how discipline-based educational research is helping to assess learn- ing in BMB students. A number of present- ers discussed alternative teaching strategies for use in the classroom includ- Teaster Baird Jr. from San Francisco State University leads participants in developing education action plans.

50 ASBMB TODAY OCTOBER 2015 Conference attendees at the Wyeth Tootle Mansion in St. Joseph, MO., for a networking dinner. ing case studies (Annie Prud’homme- Renoe of the University of Missouri plans. Genereux, Quest University); focused on using broader impacts to Conference organizers included molecular visualization (Tim Herman transform undergraduate education. Quinn Vega of Montclair State Uni- and Margaret Franzen, Milwaukee Informal networking is a key ele- versity, Mary Huff of Bellarmine Uni- School of Engineering); and quantita- ment of the symposium series, and versity and Ben Caldwell of Missouri tive biology methods (Johan Paulsson, additional activities like an ASBMB Western State University, who are all Harvard University Medical School). Student Chapters luncheon helped regional directors of the ASBMB Stu- Several presenters focused on effec- facilitate more formal networking dent Chapters program. The contribu- tively integrating research into the among faculty from the same regions tions of the entire ASBMB Student curriculum. Todd Eckdahl of Missouri of the country. Chapters Steering Committee were Western State University discussed the A memorable and unique interac- essential to the planning and success use of synthetic biology, Christopher tive theater presentation from the of this meeting. Shaffer of Washington University in Chapel Hill, N.C. group “Theater Delta” was a conference highlight. Ben Caldwell (caldwell@ St. Louis talked about bioinformatics, missouriwestern.edu) is a and Joe Provost of the University of Performers took on ethical dilemmas professor of chemistry and dean San Diego offered a presentation on facing undergraduate and graduate of the Graduate School at Missouri research-based laboratory courses. students and faculty research advisors Western State University. He is including cheating, plagiarism and also a regional director of the ASBMB Student Regina Stevens-Truss of Kalama- Chapters program. zoo College led a workshop on the unauthorized collaboration. Following each scene, the audience got a chance Mary Huff (mhuff@bellarmine. ASBMB’s Hands-On Opportunities edu) is an associate professor to Promote Engagement in Sciences, to quiz the characters about their situ- of biology and assistant dean of or HOPES program, which fosters ations and motivations. Bellarmine University’s College of outreach partnerships between BMB Post-conference surveys revealed Arts and Sciences in Louisville, 97.7 percent of attendees achieved KY. She is also a regional director of the ASBMB researchers and K–12 teachers in their Student Chapters program. local communities. And Angela Klaus their conference learning goals and would recommend this conference in Quinn Vega (vegan@mail. of Seton Hall University focused on montclair.edu) is a professor and the future. Participants were pleased National Science Foundation funding chairman of the department of to learn active strategies for the class- Biology at Montclair State Univer- opportunities for primarily under- room and happy with the conference’s sity. He is also a regional director graduate institutions, while Susan emphasis on open dialogue and action of the ASBMB Student Chapters program.

OCTOBER 2015 ASBMB TODAY 51 OUTREACH Drinks, chips and STEM Rockville’s young adult science café is a win-win By Tin Lok Wong

uring the 2014 – 15 aca- offer sneak peeks into potential break- roles and find where she or he belongs demic year, groups of middle throughs in their fields. in the future, we found the best way D school, high school and college Mitra Nusraty, an honorarium is to meet scientists doing those jobs. students gathered after hours in a committee chair for YA, has seen Our location helps. We are for- classroom at the Universities of Shady scientist–student interactions go very tunate to be in Rockville, Md., one Grove in Rockville, Md., to munch well. “Sometimes, students hesitate of the world’s centers for scientific on snacks and spend some time with to ask questions because they are research and a town that is just down local scientists. Participants in a series shy. However, we the undergraduates the road from the National Institutes called the Young Adult Science Café, know what questions to ask because of Health. Our February speaker, or YA, the group heard presentations we once had these questions within David J. Spiro, who is the influenza and engaged in informal discussions ourselves! It makes us extremely section chief at the NIH, remarked meant to create dialogue, promote happy whenever we see students that Rockville is one of the most interest in and awareness about approach our speakers during the resource-filled cities in the United STEM, and provide opportunities for break session or after the talk. This States for STEM careers. He felt that any would-be scientists in attendance means that we are creating opportuni- students interested in STEM fields to hear insiders’ takes on potential ties — dialogues for these students should take more advantage of those science careers. that we wish we once had,” she says. resources. Michelle Aroyo–Perez, who A program of the Rockville Sci- Now that the café has been run- is YA’s treasurer, says that’s part of our ence Center that is organized by the ning for a few years, it’s clear we are group’s mission. “We would like to American Society for Biochemistry connecting supply and demand. We ensure young scholars can have access and Molecular Biology student connect passionate scientists who are to these valuable resources within the chapter of the Universities at Shady eager to educate with students who community so that the community Grove, the YA series was initiated by want to know what it takes to be a can grow continuously as a whole.” ASBMB member Edward Eisenstein scientist. Attendees learn from speak- Six talks were held at the Uni- in 2012. We chapter organizers keep ers, organizers gain leadership experi- versities at Shady Grove over the it going, motivated to create oppor- ence and opportunities to network 2014 – 2015 academic year. Our tunities that we wish we would have with scientists, and speakers are able final gathering took place off campus: had when we were in high school. to do public outreach and encourage a talk and tour of the hottest new Back then, we might have known we the next generation of STEM profes- labs at the Germantown Campus of were interested in science but rarely sionals. As Nana Anguah-Dei, YA Montgomery College co-hosted by had opportunities to interact with chapter vice president, says, “We are James Sniezek, Montgomery College’s a scientist and never got the chance all learning!” collegewide dean of chemical and to explore and understand different Through YA, we strive to provide biological sciences. We see a future career paths within STEM. We also clarification on the role of a scientist. opportunity to expand YA to all three understand that interacting with sci- In 2014 – 2015, students learned that of Montgomery College’s Maryland entists can be very intimidating. We scientists not only perform bench campuses. developed the program to be informal work in a laboratory but also work as The YA series starts up again in so that students comfortably can take grant writers or reviewers for orga- October. advantage of the opportunity to meet nizations that allocate funding for scientists and satisfy their curios- various research projects, experts on ity about STEM careers. Featured the world stage who combine global Tin Lok Wong has a bachelor’s degree in biological science from scientists make a special effort to be efforts to prevent pandemics, or even the University of Maryland. He was approachable. Some have debunked educators who mentor and nurture president of the ASBMB student myths related to their specialties, and generations of new scientists. In order chapter at the Universities at they often tell funny anecdotes and for each student to understand these Shady Grove from 2013 to 2015.

52 ASBMB TODAY OCTOBER 2015 Upcoming ASBMB events and deadlines

Oct. 14: Poster abstract deadline for ASBMB Special Symposium Kinases and Pseudokinases:

OCT. Spines, Scaffolds and Molecular Switches, San Diego Oct. 27: Registration deadline for ASBMB Special Symposium Kinases and Pseudokinases: Spines, Scaffolds and Molecular Switches, San Diego Oct. 24: ASBMB workshop Developing and Sharing Best Practices: From Concept to Classroom, St. Mary’s, Minneapolis Oct. 29 – 31: Society for Advancement of Hispanics/Chicanos and Native Americans in Science (SACNAS) National Conference, Washington, D.C.

Nov. 5: Abstract submission deadline for ASBMB 2016 Annual Meeting, San Diego Nov. 12: Travel award application deadline for the ASBMB 2016 Annual Meeting, San Diego NOV. Nov. 11 – 14: Annual Biomedical Research Conference for Minority Students (ABRCMS), Booth #900, Seattle Nov. 21: ASBMB workshop Developing and Sharing Best Practices: From Concept to Classroom, San Diego

Dec. 1: Deadline for 2017 Special Symposia proposals Dec. 5 – 8: ASBMB Special Symposium Kinases and Pseudokinases: DEC. Spines, Scaffolds and Molecular Switches, San Diego

OCTOBER 2015 ASBMB TODAY 53 Sample ASBMB Abstract Topic Category Titles (#2000-2697)

• Bioinorganic Catalysis • Cell Signaling, Kinase and Chemotheraphy • Chemical Biology and Drug Discovery • Chromatin Organization and Gene Regulation • DNA Replication, Repair and Recombination Abstract submission • Education and Professional Development deadline: Nov. 5 • Glycoscience in Biology • Lipids and Lipid Signaling Travel award application • Metabolism, Disease and Drug Design deadline: Nov. 12 • Non-Alcoholic Fatty Liver Disease • Post-translational Modifications ASBMB members can save • Protein Synthesis and Degradation up to 56% on MEETING COSTS! • Recent Advances in Protein Engineering • Systems Biology and Proteomics www.asbmb.org/meeting2016