2021 Early June - science.nichd.nih.gov
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2021 Early June The OSD News Bulletin is an evolving platform that may include other features in the future. If you have any items that you would like to submit for our , please contact Dr. Triesta Fowler at Congrats and Kudos section or if you would like to request specific items to be included in the bulletin [email protected]. Click the image to download the announcement PDF (786 kB). For a text transcript, click the following link: Affinity Group Spotlight Announcement May/Early June Spotlight: Cell and Structural Biology (Banerjee lab)
Transcript of 2021 Early June - science.nichd.nih.gov
2021 Early JuneThe OSD News Bulletin is an evolving platform that may include other features in the future. If you have any items that you would like to submit for our
, please contact Dr. Triesta Fowler at Congrats and Kudos section or if you would like to request specific items to be included in the bulletin [email protected].
Click the image to download the announcement PDF (786 kB). For a text transcript, click the following link: Affinity Group Spotlight Announcement
May/Early June Spotlight: Cell and Structural Biology (Banerjee lab)
Autophagy is a catabolic process conserved from yeast to humans involving capture of cytoplasmic materials into double-membraned autophagosomes that fuse to lysosomes lead to subsequent degradation of the encapsulated materials. Autophagy is involved in a range of physiological processes, including survival under conditions of nutrient deprivation and the clearance of protein aggregates, damaged organelles and intracellular pathogens. Yet, how the different components of the core autophagy machinery lead to the formation and expansion of the double-membrane structure of the autophagosome is poorly understood. ATG9 is the only transmembrane protein in this core autophagy machinery and is essential for autophagy. However, a high-resolution structure of ATG9 was a key missing piece that we set out to obtain. Human transmembrane proteins are difficult targets for obtaining high-resolution structures which is why this remained an unsolved problem.
We solved a high-resolution structure of human ATG9A, which revealed that this protein has a wedge-shaped structure with a novel fold not seen thus far in any membrane proteins. ATG9 forms a tightly intertwined trimer in the membrane, with a large extramembranous cytosolic domain. Intriguingly, the trimeric structure contains a network of connected cavities that run through the protein, suggesting a role in phospholipid translocation across the bilayer. In
experiments revealed that cavity-lining residues are indeed important for ATG9A function. Furthermore, structure-guided computations revealed cellulothat the ATG9A trimer has a propensity to bend the bilayer. These results are consistent with observations that ATG9 localizes to highly curved membranes and offered a solution to the longstanding problem of how lipids arriving at one leaflet of the autophagosome distribute over the two monolayers.
Click image to view larger.(A) Cryo-EM density map of human ATG9A is shown in side and top views and colored according to the protomer (cyan, magenta, and orange). Dark gray represents density without assigned sequence, and translucent surface shows disordered detergent molecules surrounding the transmembrane surface of the trimer. The edges of the membrane are shown as gray lines.
(B) Topology of the human ATG9A protomer showing numbered a helices as rounded rectangles and b strands as filled arrows.
(C) Structure of an isolated protomer of human ATG9A (cyan) and two a helices from another protomer (magenta). Numbers correspond to a helices.
(D) Electrostatic potential surface of the human ATG9A trimer showing a slice through the protein and the cavities running through the protein—central pore, lateral branch, and perpendicular branch. The electrostatic potential scale is shown below the molecules, from negative values (2 k T/e) in red, to positive values (+2 k T/e) in blue.B B
(E) (Top) Confocal microscopy of WT and ATG9A-KO HeLa cells immunostained for endogenous LC3B. Notice that ATG9A KO results in the appearance of large, bright LC3B puncta in the cytoplasm (arrows).(Bottom) ATG9A-KO HeLa cells were transfected with plasmids encoding GFP-tagged ATG9A constructs (1–522 or R422W as indicated in figure) and immunostained for endogenous LC3B. Transfected cells are indicated by the dashed outlines. Scale bar: 10 mm. Notice that these two mutants cause similar appearance of large, bright LC3B puncta indicating malfunctioning of the autophagy pathway.
This research addressed a key missing piece in our understanding of the structure and mechanism of the autophagy machinery, which had been shrouded in mystery for a long time. ATG9 is an important protein interaction hub for the autophagy pathway and our high-resolution structure will be the starting point for many future experiments rooted in the atomic resolution information about ATG9 that has become available now. Since publication, other labs have substantiated our hypothesis that ATG9 is a lipid translocase, answering an unresolved puzzle as to how lipids get distributed across both leaflets of the autophagosomal membrane. Finally, autophagy is critically important in human diseases such as neurogenerative diseases and cancer. Our research will help unravel the molecular insights into how malfunctions in ATG9 could contribute to that as disease mutations are discovered.
Click image to download video (MP4, 175MB)Molecular Dynamics Simulation of a hypothetical ATG9A Cluster in a POPC Bilayer, The video depicts the time-evolution of the membrane in a calculated trajectory of 1 s. ATG9A proteins are shown in gray, and lipid molecules in colors—both represented with a coarse-grained forcefield and diffusing freely in the course of the trajectory.
References
Carlos M Guardia*, Xiao-Feng Tan*, Tengfei Lian*, Mitra S Rana*, Wenchang Zhou, Eric T Christenson, Augustus J Lowry, José D Faraldo-Gómez, Juan S Bonifacino , Jiansen Jiang , and Anirban Banerjee (2020). Structure of Human ATG9A, the Only Transmembrane Protein of the Core Autophagy † † †
Machinery. , (13), 107837. (*= contributed equally; = co-corresponding authors).Cell Reports 31 http://doi.org/10.1016/j.celrep.2020.107837 †
Carlos M Guardia*, Eric T Christenson*, Wenchang Zhou, Xiao-Feng Tan, Tengfei Lian, José D Faraldo-Gómez , Juan S Bonifacino , Jiansen Jiang , and † † †
Anirban Banerjee (2020). The structure of human ATG9A and its interplay with the lipid bilayer. , (12), 2292–2293. † Autophagy 16 http://doi.org/10.1080 (*= contributed equally; = co-corresponding authors)/15548627.2020.1830522 †
NICHD, DIR Mandatory Training Calendar
Annual Training
1.
2.
Spring
Training Title Audience Duration Estimated Deadline Delivery
Whistleblower Protection and Prohibited Personnel Practices Supervisors 60 minutes ~April LMS
Implicit Bias All Staff 60 minutes ~May LMS
Summer
Training Title Audience Duration Estimated Deadline Delivery
Information Security and Management Refresher All Staff 60 minutes ~June Online
Fall
Training Title Audience Duration Estimated Deadline Delivery
USERRA (Uniformed Services Employment and Reemployment Rights Act) Supervisors 60 minutes ~September LMS
VET (Veteran Employment Training) Supervisors 60 minutes ~September LMS
Winter
Training Title Audience Duration Estimated Deadline Delivery
NIH Anti-Harrassment Training (NO FEAR/POSH) — Online EEO Training All Staff 90 minutes ~December LMS
Ethics Training Refresher All Staff 30 minutes ~December Online
Training Required Every 3 Years
Training Title Audience Duration Estimated Deadline Delivery
NIH Bystander Training (Supervisor & Non-Supervisor Specific Training All Staff 2 hours December 31 Webinar
NIH Supervisor Refresher Training Supervisor 16 hours December 31 LMS
Responsible conduct of research (RCR) Training – Deadline June 30, 2021
All NICHD scientists (PIs, staff scientists, postdocs, postbacs, graduate students, visiting fellows, contractors, etc.) are required to participate in dtwo hoursiscussion based RCR training. Virtual offerings are highly recommended.
Annual Discussion of Research Ethics Cases (1 hr., affinity group level) provided by Building 1 are found at https://oir.nih.gov/sourcebook/ethical-. The 2020 theme was recently added to the OIR sourcebook: conduct/responsible-conduct-research-training/annual-review-ethics-case-studies
Data, Project and Lab Management, and Communication. These discussions should take place at the affinity group level. It is important that all affinity group facilitators provide the Office of Education with the session information in advance(date, time, facilitator’s name, and Zoom/WebEx link). This will allow others in DIR to join if they are not able to participate in their own affinity group session.
Annual Discussion of Reproducibility of Data/Ethical Research in My Lab (1 hr., individual group level). Since these discussions should take place at the individual lab group level, you can be more flexible in preparing your training session. OIR has provided four videos with associated
as a resource, or you can discuss limitations of experimental approaches commonly used in the lab or retracted papers in discussion questions your specialized field ( or a similar website). For this reproducibility discussion, you can always receive credit for http://retractionwatch.com leadership training.
The Office of Education will be tracking the participation for these two trainings as required by Bldg. 1, and our goal is to reach over 90% compliance within the DIR.
Please send Carol Carnahan ( ) your attendance list by email, for the two training requirements noted above. It should include the [email protected] lab staff names, the training date, and which training requirement it was for (Ethics Cases or Reproducibility).
Make up sessions for both requirements will be offered in early 2021; please contact Dr. Erin Walsh at if you have any specific [email protected].
All timelines are estimated and subject to change.
This list is meant to be used as a guide and is a comprehensive list of HHS/NIH/NICHD training requirements.NOT
For more information, please visit the NIH Mandatory Training Inventory: https://hr.nih.gov/training-center/mti/mandatory-training-inventory
Check back next month!
Check back next month!
Check back next month!
End of the Year Procurement Deadline
In an effort to assist with FY2021 budget planning, below are the End of Year procurement submission deadline dates: see chart below.
Please keep the following in mind when preparing your POTS requests:
All POTS requests must be submitted to your Administrative Officer (AO) by the COB on the deadline date in the chart below.All POTS requests should include a detailed justification.
Justifications like “supply,” “chemical” or “for lab use” or “lab supply” or “for research experiment” should not be used.Micro-Purchase threshold is under $5,000 (must include all charges such as shipping & handling, dry ice, inside delivery, etc.)Requests over the Micro-Purchase threshold, $5,000 and above, require additional documentation:
Narrative justifications for sole source will not be accepted and the POTS will be returned for the required JOFOC form.Vendor quote(s) from competitive sourcesMarket research: list of all vendors contactedIf Sole Source, please include the required JOFOC form; JOFOC form must be completed and signed (contact Sylvia Robinson at 301-
827-4346 or [email protected] for the forms).Trade-Ins: If the quote references a trade-in credit, the trade-in form is required for all Government owned property; this form must be completed and signed (contact Sylvia Robinson at 301-827-4346 or [email protected] for the forms).
For any approved request over $250,000, please contact Sylvia Robinson at 301-827-4346 or as soon as possible so that we [email protected] assist with a strategic plan for processing your order and if you need the Acquisition Strategy and Acquisition Plan form that is required for requests at this dollar level.
Dollar Thresholds Deadline Dates
Equipment, Supplies, and Services $25,001–$250,000 5/28/2021
$15,001–$25,000 6/30/2021
$10,001–$15,000 7/30/2021
$10,000 and less 8/6/2021
$5,000 and less, P-Card only 8/27/2021
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2021 NICHD Director's Early Career Awards
This program, which was formerly the , is part of NICHD OD’s ongoing programs to develop the scientific workforce in NICHD Young Investigator Awardspromotion of NICHD’s mission and our most recent strategic plan. Fifty applications were received, and we were able to fund 22. Awardees will be notified by the OSD, and all applicants will receive the reviewers’ feedback on their proposals. Below is detailed information about how the applications were scored and how the funds will be distributed.
Explanation of Comments and Scoring:
The proposals were reviewed by a committee of seven NICHD investigators that included experts in neurobiology, membrane biology, development, genetics, epidemiology, and clinical research.Each proposal was evaluated for strength in three areas:
Productivity and credentials of candidate relative to career stageImpact of proposal on career development of the candidateScientific merit of proposal
Each of the three criteria was assigned a score of 1 to 5.Each reviewer provided brief comments highlighting strengths and weaknesses.
Funding Distribution:
After scoring, the proposals were divided into three categories:Basic science (36/50 proposals)Epidemiology/Population Health (3/50 proposals)Clinical Studies (11/50 proposals)
The total funding ($390,000) was divided between these categories in proportion to the number of proposals within each category.Within each category, the funds were distributed according to the rankings from the review committee.
We were able to fund 14 basic science applicants, 3 Epidemiology/Population Health applicants, and 5 clinical applicants.
To download the official announcement, please click here: (123 KB)NICHD Early Career Awards Announcement 5-11-21[1].pdf
NIH’s Return to Work Guidance
The NIH Return to Work Guidance was updated in April 2021. Below is the list of changes from the previous version. Full version of the updated guidance here: (2.2 MB)Return-to-Work-Guidance April 2021[1].pdf
Reduced population limitations from one (1) person per 200–250 net square feet to one (1) person per 125 net square feet (pg. 17). Changes in density do not impact numbers of persons allowed in buildings or campuses, as those numbers are predetermined by a waiver request regarding an Executive Order. Increases in allowed density are based on:
Increased vaccination rates among NIH staff and within the communityIndustry trends from other premier biomedical research institutions (e.g., Johns Hopkins University) regarding higher population allowances.
Section on conducting Activity Hazard Analyses (AHAs) (pg. 12)NIH operations require AHAs to ensure risks are minimized. This version provides guidance on how to conduct required risk assessments.
Updated guidance on travel and post-travel requirements (pgs. 7–12)Travel guidance was updated to clarify guidelines for return to work after traveling.Updated guidance expedites return to work for personnel that have been vaccinated.Updated guidance for international and domestic RTW expectations
Improving Fit and Filtration of face coverings. Includes information on the knotting and tucking technique, mask fitters/braces, and double masking (pgs. 15–17).Information on site visits from outside organizations (e.g., AAALAC, BSAT, etc.) (pg. 23)Updates to Appendix IV to include information on improving mask fit during close proximity work (pg. 31–36)Updates to Appendix V to reflect knotting and tucking technique, double masking, and mask fitters. Also update to reflect change in Division of Logistics Services (DLS) website which prevents direct link to products from previously hyperlinked recommended equipment. (pgs. 36–37)Addition of Appendix VI which describes the knotting and tucking technique for surgical masks (pgs. 38–39)Addition of Appendix VII – Selection, Use, Care, and Storage of Mask Fitters/Braces (pgs. 40–41)Vaccine related information and post vaccine safety requirements (pg. 6–7)
Getting to know: NICHD Office of Communications
Did you know? You can share your scientific findings with broader, public audiences through NICHD’s social media platforms. If you’d like to feature your scientific image, publication, or other content, contact the NICHD Office of Communications at . A member of the office, Linda [email protected], Ph.D., will also give an overview of science communications at the PI meeting in May.
Early Career Award Recipients
Clinical Research
Jacqueline Yano MaherAnna ZennoAn Ngoc Dang Do Katerina Hadrava Vanova Maziar Rahmani
Basic Research
Raffaella De PacePhilip Patrick AdamsThien NguyenMohamed Mahgoub Mohamed Huu NguyenDoreen Matthies Aoshu ZhongRachel Leigh CosbyJarred Whitlock Melania BrunoLucia Bettedi Aisha Tafa Burton Rilee ZeinertLee Hyungchul
Epidemiology
Kristen J. Polinski Susanna Mitro Jenna Rosemarie Cummings
Current Edition of the NICHD Director’s Newsletter (May 2021)
NICHD email address for questions about COVID-19
The NICHD Office of the Clinical Director has set up an email address for any questions you may have about CDC guidelines, quarantine recommendations, or NIH policies related to COVID-19. The goal is to help reduce the number of calls to the NIH Occupational Medical Service. If you have broad questions about COVID-19, you can send them to , and NICHD clinical staff will [email protected]
NIH Guidance for Staff on COVID-19: https://employees.nih.gov/pages/coronavirus/index.aspx
NICHD Insider guidance on COVID-19: https://insider.nichd.nih.gov/director/Pages/NICHD-COVID-19-information.aspx
Staff is encouraged to take advantage of on the 5 floor of the NIH Clinical Center—even if you’ve been vaccinated. SARS-CoV2 testing th
Testing is available every day but Wednesday during the work week, and for Clinical Center staff who work on the weekend. You can schedule for your test or just walk-in. Drive through symptomatic testing (“the carline”) is now available on Tuesdays and Thursdays only.an appointment
SARS-CoV2 vaccination clinic in the B1 Cafeteria of the NIH Clinical Center is offering appointments through June 10 . After June 10, staff th
will have to schedule an appointment for themselves in the community. For those who have been vaccinated in the community, please be sure to let us know by reporting it through .this online form
COVID Notes
Reminder to staff that they are expected to . This practice is wear masks while on campusa courtesy to your co-workers and is essential to safety of our community.
Those interested in a detail as a should contact the OSD. Please secure the approval of your supervisor contract tracer in the Clinical Centerprior to volunteering. Note that this detail will entail a substantial full-time commitment, including a required training that is over a week.
In case you missed it: Persistent COVID-19 Information
Current Edition of the Deputy Director for Intramural Research's Web Board
For , check out this month’s fellows newsletter, . Trainee Highlights , Volume 12, Issue 132The NICHD Connection
2021 Developing Talent Scholars Awardees
Andrea Munoz (Dang Do)Tiara Tillis (Storz)
2021 Fellowship Recruitment Incentive Awardee (FRIA)
Dr. Todd Macfarlan – in support of Mohamed, Mohamed Mahgoub
2021 Intramural Research Fellowship Awardees
Dr. Alan Kessler (Maraia)Dr. Gergo Gulyas (Balla)Dr. Thien Nguyen (Gandjbakhche)Dr. Anna Dorothea Senft (Macfarlan)
Center on Compulsive Behaviors Fellowship Awardees 2021
Dr. Thien Nguyen (Gandjbakhche)Dr. Adam Caccavano (McBain)Dr. Geoffrey Vargish (McBain)Dr. Wen-Chieh Hsieh (Serpe)
from the Dr. Karel Pacak Developmental Endocrinology, Metabolism, Genetics & Endocrine Oncology (DEMGEO) Affinity Group – Section on Medical received the Outstanding Clinical Investigator Award as one of Laureate Awards from the US Endocrine Society. He was also elected Neuroendocrinology
as the member of the Czech Medical Academy.
