The NICHD Thirteenth Annual Meeting of Postdoctoral, Clinical, and Visiting Fellows and Graduate Students took place on May 1, 2017, at the National Museum of the American Indian in Washington, D.C. This year, the event included a morning keynote by Nobel Laureate Dr. Peter Agre, three outstanding presentations by NICHD fellows, nine round table career discussions, presentations by several of our Three-minute-Talk competitors, and an entertaining career keynote by comedian Dr. Adam Ruben.
Several fellows who attended the event recapped the talks for The NICHD Connection. We are excited to bring you the 2017 Annual Fellows Retreat presentations. Enjoy!
View more photos from the retreat here: 2017 Fellows Retreat Photos
Dr. Peter Agre and His “Facebook of Science”
By Kathryn Tabor, PhD
Dr. Peter Agre, director of the Malaria Research Institute at the Bloomberg School of Public Health, spoke during the 2017 NICHD Fellows Retreat keynote about how the people in his life shaped his career. Family, colleagues, local leaders, and scientists from around the world proved instrumental to his life in science.
During his biomedical studies at Johns Hopkins University, Agre saw first-hand that people from disparate and often opposing cultures around the world—a Spanish immigrant, a Palestinian from Lebanon, a Jew from Brooklyn, and an Italian film actor—could become close friends through working together in the lab. These colleagues proved essential to his discovery of the water channel, aquaporin, for which he won the 2003 Nobel Prize in Chemistry.
The story began while he was searching for the molecular identity of the blood group antigen Rh. Frustrating his attempts to isolate Rh was a second amazingly abundant membrane protein. The sequence of this mystery protein was related to proteins from diverse species, but with no known function. Agre’s friend, Dr. John Parker, excitedly asked if this mystery protein might be the long-sought water channel.
The Agre lab tested this by overexpressing the protein in frog eggs. When placed in water, the oocytes exploded rapidly “like popcorn,” which triggered jubilation in the lab and launched a new phase of research. The discovery of the intensely hunted water channel, aquaporin 1, spurred key collaborations both locally and around the world. Research focused on resolving the aquaporin family members and their expression patterns, biophysical functions, structures, and roles in health and disease.
While his father, a chemistry professor, encouraged him to pursue a science career, his mother, committed to the well-being of others, urged Agre to use his talent for the welfare of those in need.
Agre decided to focus his research on aquaporin in malaria. Aquaglyceroporin, a type of aquaporin, provides the pathway for glycerol uptake into the malaria parasite. Aquaglyceroporin-null parasites are deficient in glycerol uptake, hindering proliferation, which makes this protein a promising target for antimalarial drugs. As Director for the Johns Hopkins Malaria Research Institute, he established field stations in Zambia, Zimbabwe, and Congo, where malaria is epidemic, especially in children. Through building connections with local community leaders and researchers, his fieldwork significantly reduced the malaria burden in Zambia.
Agre ended the keynote with a few stories about his travels as President of the American Association for the Advancement of Science, a role in which he served from 2009 to 2010. At the time, a new program of science diplomacy had been developed, sending American scientists to visit scientists in other countries. He recounted his meetings with the president of Cuba, Fidel Castro, and the former Iran minister of foreign affairs, Ali Akbar Salehi—both scientists. In both encounters, though they disagreed on many things, the importance of science and the benefits of healthcare were two issues they agreed on wholeheartedly. Even during his difficult visit to North Korea, he met talented scientists with shared ambitions.
Agre proposed that science diplomacy is simply making contact and developing human networks around the world. He said “looking back, it is the people that [he] met along the way that are just as important as the science.”
BORC, It’s Like an Uber for Lysosomes
By Fatima Chowdhry, MD
Lysosomes, cellular organelles found in the cytoplasm, contain enzymes known for their degradative properties. One aspect of lysosomal functioning that has gained traction in the past few years is lysosomal positioning in relation to cellular distribution and movement. Lysosome positioning can change due to nutrient availability. With nutrient abundance, the lysosomes distribute throughout the cell. When nutrients are deficient, they cluster around one area. It is not clear why lysosomes change their position, but it may be due to metabolic signaling.
Dr. Jing Pu, a postdoctoral fellow in Dr. Bonifacino’s lab, identified the BLOC-One Related Complex (BORC). This complex consists of eight small proteins and regulates lysosomal positioning. It helps to direct lysosomes from the center of the cell to the periphery, which means that the ability of lysosomes to move throughout the cell is diminished in cells lacking BORC due to a deletion.
This research has relevance to a critical disease—cancer. Metastatic cancer cells are aggressive and invade other tissues. Lysosomes release their enzymes outside the cell to digest extracellular matrix and promote cell migration. If there were a BORC block, then lysosomes would be unable to position themselves throughout the cell to release enzymes into the extracellular matrix, potentially limiting cancer cell migration.
Pu’s latest research discovered how BORC regulates lysosome positioning by recruiting the small GTPase Arl8 to the lysosome surface, thus promoting kinesin-dependent movement of lysosomes toward the cell periphery. Pu emphasized that amino acids are important nutrients that regulate lysosome positioning, and she will continue to focus on how amino acids regulate interaction between BORC and Ragulator, a protein complex known to interact with specific GTPases.
With Help from Scd6, mRNA May Play a Role in its Own Fate
By Allison Dennis
The cell generates more messenger RNA (mRNA) than is necessary to maintain the proper assortment of proteins. But what happens to the unnecessary mRNA? Destroying it is an absolute solution; however, preventing it from reaching the translational machinery is a tunable solution, allowing the flexibility to respond as demand for mRNA changes.
Dr. Quira Zeidan, a postdoctoral fellow in the Hinnebusch lab, is unraveling how the binding and dissociation of key protein players can sway the balance of an mRNA’s fate. Zeidan is focusing on Scd6, a protein player that has been shown in vitro to play a role in two mRNA paths: degradation (by binding a decapping enzyme complex, leading to mRNA decay) and translation blocking (by blocking ribosome recognition).
Zeidan developed a system to evaluate the outcomes of mRNA that associate with Scd6 in vivo. In the system, Zeidan tricked Scd6 into binding a specific mRNA. She fused Scd6 to a protein with a known mRNA binding sequence, and she inserted that sequence in front of the GFP and lacZ reporter genes. Zeidan monitored changes in GFP or lacZ expression and compared those changes to mRNA levels.
Surprisingly, the fates of each in vivo reporter highlighted a different facet of the activities implicated for Scd6 in vitro. Tethering Scd6 to the lacZ mRNA resulted in reduced protein expression without any observation of mRNA decay, a finding dependent on the DEAD-box RNA helicase Dhh1. In contrast, tethering Scd6 to the GFP mRNA lead to both reduced protein and mRNA levels, which required the decapping enzyme, Dcp2 as well as Dhh1.
Zeidan’s research revealed a valuable lesson from a seasoned experimentalist. When Zeidan began planning her experiment, the GFP reporter plasmid was readily available, but she recognized the lacZ gene could give more quantifiable results. Instead of waiting, she hit the bench to first unravel the story using the less-than-ideal GFP reporter while continuing to develop the LacZ expression system. Upon following up with the lacZ reporter, what could have been a redundant experiment turned into a very elegant story: the ultimate fate of Scd6 bound mRNAs is not the same for all mRNAs in vivo, opening the door to further exploration.
New Method of Mapping Nucleosomes
By Copelan Gammon
A single human cell contains about two meters of DNA; the human body is estimated to contain 100 trillion meters of DNA. Dr. Razvan V. Chereji puts this in perspective for the audience of the annual NICHD Fellows Retreat, saying this is “enough to go from here to the sun and back more than 300 times.” Mapping nucleosomes, the basic unit of DNA packaging, presents a significant challenge—one that Chereji addresses with new methodology and predictive modeling.
Chereji, a research fellow in Dr. David Clark’s lab, the Section on Chromatin and Gene Expression, is interested in the intersection of theoretical physics and quantitative biology. Chereji earned a PhD in physics from Rutgers University and ultimately wants to apply his training in rigorous computational techniques to traditional biology to better understand gene expression regulation and chromatic organization.
Chereji’s current research has yielded a new method of mapping both single nucleosomes and linkers of neighboring nucleosomes within the same cell, in vivo. Nucleosome positions have a strong effect on all DNA-related processes. This new method of chemical mapping produces precise, high-resolution results compared to the commonly used MNase-seq, which combines chromatin digestion with pair-end sequencing. Using statistical mechanics, Chereji and his colleagues successfully created a predictive model of genome-wide nucleosome organization in yeast.
Finding Your Passion in “Purgatory”
By Zelia Worman, PhD
Our afternoon keynote speaker, Dr. Adam Ruben, earned a PhD in Biology from Johns Hopkins University, but he may be best known for his book “Surviving Your Stupid, Stupid Decision to Go to Grad School.” He is a comedian, participant in the science channel show Head Rush, writer for a Science Careers humor column, and the associate director at Sanaria, a biotech company with the mission to eradicate Malaria through vaccination. Although he began his talk describing his grad school experiences, he immediately made the leap to how he became successful through a fun combination of coincidences, luck, and hard work.
One of the most hilarious moments of his talk was when he articulated a generalized postdoctoral sentiment: a postdoc is a temporary position (that he called purgatory) that’s supposed to lead to an assistant professor job, where the other alternative is just failure. He stated that this can’t be the culture in science when only 15% of PhD graduates get a position as a professor. “Alternative career” is not so alternative anymore.
Complications begin when we realize that academic positions are limited for scientists, but we are encouraged to get kids interested in STEM fields to become future scientists. The problems continue when we fail to train these kids to remain in STEM, even if they’re not interested in academia and would instead like to explore different fields, such as writing, policy, patent law, etc.
According to Ruben, the training culture of graduate school and postdoctoral studies needs to change so that young minds, amazed by the cool guy that freezes a banana in liquid nitrogen, avoid feeling stuck and disappointed after years of hard work and studying. He argues that we shouldn’t end up looking at ourselves after seven years and ask: how did I end up spending my time knowing things I don’t care about? Or why did I go to meetings just for the food and free beer?
Alas, this is exactly what he (and some of us) did. After seven years in graduate school, he realized that he wanted to be a scientist who does things beyond the bench, and not one that focuses on pathways and theoretical work. He pointed out there’s no wrong way of being a scientist, but we need to know which kind we are and go for it! So, he went to every meeting for the free beer and food, but he ended up meeting a person from the company he currently works at. He got married, had kids, continued with his comedy, took writing classes, and did so much more. And eventually, the combination of all the things he did and people he met along the way got him to where he is now.
From his talk, we received amazing advice on how to network (please don’t throw your business cards at strangers—connect and talk to people!), how to graduate (take control of your future and come up with a plan!), how to stand out (do things you are passionate about), and how to order super fancy incubators that “hold temperature in Celsius AND Fahrenheit” from people who have absolutely zero idea why this is funny (pun intended).
Do your thing, all the time, as much as you can. Learn new things; take a class just for fun. Be yourself, write, jog, and volunteer for something you believe in, even if it’s completely unrelated to science. It will make you stand out and make you YOU, not another resume in a pile. Experience things; get out of your postdoctoral shell and DO everything.
There’s no wrong answer… only you can know what’s best for YOU.
Three-Minute-Talk Recaps in Three Sentences
By Pushpanathan Muthuirulan, PhD
Communicating science and its relevance in three minutes, and now, in three sentences.
Afrouz Anderson, PhD
Postdoctoral Fellow, Gandjbakhche Lab
The placenta is an important organ that facilitates oxygen exchange between fetal and maternal blood, and impaired placental function is associated with fetal growth restriction and poor neonatal outcome. To address challenges in measuring placental oxygenation, Dr. Afrouz Anderson developed a new wireless portable device—called an oximeter—that uses near-infrared light to measure placental oxygen in the mother’s abdomen. This device has potential for use during preeclampsia, or when the fetus is not growing properly.
Arup Chakraborty, PhD
Research Fellow, DePamphilis Lab
Cancer is a relentless monster that can thrive in conditions that are lethal to normal cells. Dr. Arup Chakraborty, who studies the role of geminin protein in mouse embryonic stem cells, has found that geminin inhibition can selectively kill cancer stem cells, which serve as the precursors for tumor formation, metastasis, and recurrence. In future work, studying geminin function in human embryonic stem cells could uncover novel therapeutic options for fighting cancer in humans.
Hadis Dashtestani, MS
Graduate Student, Gandjbakhche Lab
Antisocial personality disorder (ASPD) is characterized by a violation of the rights of others and lack of conformity to social norms. To understand the neural basis behind ASPD, Hadis Dashtestani performed neuroimaging studies using functional near infrared spectroscopy (fNIRS) while implementing moral judgment (MJ) tasks with personality assessments of psychopathic traits in a cost-effective and patient-friendly environment. Dashtestani’s research has opened up the new possibility of classifying degrees of psychopathy in incarcerated populations based on neural activity.
Jeremy Weaver, PhD
Postdoctoral Fellow, Storz Lab
Small proteins act as regulators of larger proteins in both prokaryotes and eukaryotes, but small proteins have traditionally been overlooked due to challenges in their annotation and biochemical detection. To gain insight into small protein regulators, Dr. Jeremy Weaver uses a mass spectrometry-based proteomic approach with E. coli lysate to selectively enrich new small proteins that would likely remain undetected by other techniques. Weaver’s research provides a new path for researchers to explore the prevalence of small proteins in any type of organism or cellular components.