Newsletter Mar 2020

Announcements

  • Due to recent support generously contributed from our funding units (LSA, LSI, COP, and Med), BioNMR core is no longer charging users from University of Michigan for consultation time. However, we will continue to log the time that we spend with each user as a way of demonstrating service to users in the different units.
  • Faculty and graduate student recruitment season is continuing, so users should be aware that tour groups will be in instrument spaces.
  • The 600 MHz NMR in 3214A LSI will be completely upgraded to Prodigy cryo-probe with NEO console during April 2020.  This will significantly upgrade the capability, sensitivity, and throughput of this instrument for our users. Delivery and preparation for the install will happen during the last week of March 2020. We expect this instrument to be down Mar 23rd – April 20th 2020, so please plan experiments accordingly.
  • The University of Michigan‘s Biosciences Initiative Core Lab program recently funded a complete renovation of the Varian 600 MHz NMR 600 in 1047 Chemistry.  Read more here. The existing magnet will be converted to a Bruker instrument with a NEO console and the latest helium cooled TCI CryoProbe. As a result, this instrument will have similar capabilities and the same software as the 800 MHz instrument, facilitating usage across instruments and increasing availability. Down time for this install is anticipated in Aug 2020.
  • The BioNMR core has a new program to provide instrument time for junior faculty collecting preliminary NMR data for external grant proposals. Supported by the College of Literature, Sciences and Arts; Life Sciences Institute; College of Pharmacy; and the Medical School, application details are below.    

BioNMR core’s Exploration Funds

BioNMR core’s exploration funds will be used to provide NMR instrument time to UM junior faculty (research assistant professors and assistant professors) who need to collect preliminary data for new external grant applications. The application (https://forms.gle/ndgwQRtcDsH9w8i17) requires:

  • Qualifications of the investigator(s): Assistant professor / research assistant professor
  • Objectives and scientific/technical significance of the proposed project (1-2 paragraphs)
  • Riskiness/feasibility of methods employed
  • Details of the NMR experiments proposed (e.g. list of experiments) ~1 paragraph
  • Suitability of the methods employed
  • Amount of NMR time and instrument requested to carry out proposed projects

Applications will be reviewed by BioNMR core staff and evaluated by the BioNMR advisory committee on a quarterly basis.

Upcoming NMR Conferences

NMRlib 2.0 : IBS pulse sequence tools for Bruker spectrometers available on NMR 800

The NMRlib package contains a suite of jython-based tools designed for Bruker spectrometers (TopSpin versions 3.2–4.0) that allow easy setup, management, and exchange of NMR experiments. A NMR experiment can be set up and executed in a few clicks by navigating through the NMRlib GUI tree structure, without any further parameter adjustment. We now have working versions of all sequences mentioned in the latest paper A Favier and B Brutscher. NMRlib: user-friendly pulse sequence tools for Bruker NMR spectrometers (2019) J Biomol NMR. 73(5), 199-211. (details: https://link.springer.com/article/10.1007%2Fs10858-019-00249-1) Please contact BioNMR core staff to get help with setting up these experiments.

NMR Technique Highlight: A better isotopically labeled NMR Sample preparation protocol

The authors here present a modified minimal medium and a simple protocol that can increase the protein yield up to fourfold in a pH-stabilized LB medium and up to seven-fold in a modified M9+ medium. Details of the paper can be found in the link below:Cai M., Huang Y., Craigie R., Clore G.M. A simple protocol for expression of isotope-labeled proteins in Escherichia coli grown in shaker flasks at high cell density (2019) J Biomol NMR. https://link.springer.com/article/10.1007/s10858-019-00285-x

BioNMR core acknowledgement in scientific publications

A reminder to all users of BioNMR core facility users, please acknowledge the BioNMR core facility for all publications that use data collected in our facility.

Research reported in this publication was supported by the University of Michigan BioNMR Core Facility (U-M BioNMR). U-M BioNMR Core is grateful for support from U-M including the College of Literature, Sciences and Arts, Life Sciences Institute, College of Pharmacy and the Medical School along with the U-M Biosciences Initiative. 

This helps us to keep track of our facility usage that leads to publications and justification for securing future funding for instrument upgrades

BioNMR core receives Biosciences Initiative Award to upgrade 600 MHz spectrometer housed in 1047 Chemistry

The University of Michigan‘s Biosciences Initiative has funded the upgrade of this instrument via the Biosciences Core Lab Funding Program read more: here. This will be updated to the latest helium cooled TCI CryoProbe with NEO console offered by Bruker Biospin

The BioNMR core assumed operations of three older NMR instruments, including a Varian 600 MHz instrument. As Varian is no longer in business, parts are more and more difficult to find and the instrument and software are no longer supported.  In order to overcome this, our proposal to Biosciences Core Lab Funding program was to reuse the newer Varian magnet at the core of this instrument and replace the console, probe, and control units to transition this to a Bruker instrument, currently the only other practical supplier of such instruments. This would ensure long-term instrument availability for the U-M research community while being a good steward of prior investment.

BioNMR core facility has been selected as one of the awardees of the Biosciences Core Lab Funding program and has been granted funds to update/upgrade the Agilent/Varian 600 MHz spectrometer with cryo-probe located in 1047 chemistry to the latest Helium cooled TCI CryoProbe, along with NEO console by Bruker. The accompanying software with this console will be Topspin 4, which can take advantage of the latest capabilities of the NEO console. In order to handle multiple samples along with automation in ICON interface, we will be equipping this instrument with Bruker’s SampleJet sample handling system. This upgrade is in the works and we will post updates as we get delivery updates from Bruker.

BioNMR core’s 600 MHz spectrometer housed in 3214 LSI building is getting an upgrade in the coming months

The University of Michigan‘s Biosciences Initiative has funded the upgrade of 600 MHz instrument via the Biosciences Research Initiative Program awarded to Natural Products Discovery Core read more: here. This will be updated to the latest nitrogen cooled Prodigy CryoProbe with NEO console offered by Bruker Biospin

In 2018, Drs. David H. Sherman and Ashootosh Tripathi (part of Natural Products Discovery Core) received funding from the Biosciences Research Initiative Program to upgrade the room temperature broadband probe connected to 600 MHz NMR spectrometer to Bruker’s latest nitrogen cooled Prodigy CryoProbe with NEO console and 24 SampleCase sample handling system.

The Prodigy CryoProbe will be ideal for routine small molecule NMR experiments, with broadband technology that covers large number of nuclei and 2-3x boost to signal as compared to room temperature probes. The ICON automation interface allows users to setup multiple experiments across many samples, and current users will be retrained to use this interface in order to use this spectrometer. This upgrade is in the works and delivery of the components from Bruker are scheduled for March/April 2020. During the upgrade users will be redirected to use the BioNMR core instruments in chemistry building.

Newsletter

Announcements

  • We welcome Dr. Minli Xing to BioNMR core facility. Minli is a protein NMR spectroscopist, her research interests include studying protein structure and function using NMR spectroscopy. Prior to joining the University of Michigan, Minli was the lab manager of the Biomolecular NMR Lab at the University of Kansas, where she operated and maintained a 600 MHz and an 800 MHz NMR spectrometer. During her work at the University of Kansas, she has developed extensive experience in protein structure determination, protein-protein and protein-ligand interaction, and STD-NMR fragment screening.
Minli Xing, Ph. D.
Senior Lab Specialist
BioNMR Core Facility
University of Michigan
Life Sciences Institute #3214
210 Washtenaw Ave, Ann Arbor MI 48109
Email: mlxing@umich.edu
Phone:734-647-1905
  • NMR 600 (LSI) will be upgraded to Prodigy cryo-probe with NEO console in the coming year, stay tuned for updates.

Gateway NMR Meeting

This year University of Michigan will be hosting the Gateway NMR Meeting (details: https://sites.google.com/umich.edu/gatewaynmr2019) on Sep 21-22, 2019. Please try to attend this meeting to meet and learn about the exciting NMR research in the area.

NMR Seminars

Advanced Capabilities of NEO console on 800 Mhz NMR instrument

The NEO console has the capability of acquiring nested NMR experiments (combining up to five conventional NMR pulse sequences into one supersequence). We have working versions of all sequences mentioned in the latest paper Kupče Ē, Claridge TDW. New NOAH modules for structure elucidation at natural isotopic abundance (2019) J Magn Reson. 307 106568. (https://www.sciencedirect.com/science/article/pii/S1090780719301855?via%3Dihub)

NMR Technique Highlight: Accelerating 2D NMR relaxation dispersion experiments using iterated maps

Conventionally relaxation dispersion data would require collection of data using the full Nyquist grid. The authors had previously developed Fourier-based reconstruction method using iterated maps according to the Difference Map algorithm of Veit Elser (DiffMap), which has been further developed to exploit the strong correlations between 2D data slices in a pseudo-3D experiment. Details of the paper can be found in the link below:

Rovny, J., Blum, R.L., Loria, J.P., Barrett S,E. Accelerating 2D NMR relaxation dispersion experiments using iterated maps (2019) J Biomol NMR. https://doi.org/10.1007/s10858-019-00263-3

BioNMR core acknowledgement in scientific publications

A reminder to all users of BioNMR core facility users, please acknowledge the BioNMR core facility for all publications that use data collected in our facility.

Research reported in this publication was supported by the University of Michigan BioNMR Core Facility (U-M BioNMR). U-M BioNMR Core is grateful for support from U-M including the College of Literature, Sciences and Arts, Life Sciences Institute, College of Pharmacy and the Medical School along with the U-M Biosciences Initiative.

This helps us to keep track of our facility usage that leads to publications and justification for securing future funding for instrument upgrades.  

Quarterly Newsletter

Announcements

  • All NMR users need to use iLabs (https://bionmrcore.umich.edu/index.php/reservations/) to reserve time and use the instrument. Please note that providing short-codes directly to BioNMR core staff will not grant access to the instruments.
  • NMR 400 (LSI) is currently down due to a sample breaking on the probe. Please use the NMR 600 (LSI) in the meantime.
  • NMR 600CP (Chem) has issues with tuning to Nitrogen and the stability of the cryo-system causing issues for experiments longer than 2 hours. The NMR facility is in touch with Varian about this issue and will update the impacted users as things get sorted out.

Recharge Rate

NMR users of BioNMR core facility, please note the latest rates for instrument usage and consultation. The rates listed below are effective Nov 20th 2018.

InstrumentU-M Rate
($/hr)
External Academic Rate
($/hr)
Corporate Rate
($/hr)
NMR 400 (LSI)$11$16.50$33
NMR 600 (LSI)$11$16.50$33
NMR 600 CP (Chem)$9.50$14.25$28.50
NMR 800 (Chem)$11.50$17.25$34.50
NMR Core Labor/
Consultation
$61$91.50$183

Seminar on advanced metabolomics analysis on NMR data

Rafael Bruschweiler from Ohio State University is presenting his recent work where they employ advanced metabolomics tools on NMR data to study protein interactions. Dr. Bruschweiler is credited for the development of Covariance NMR, which reduces the NMR measurement time for multidimensional spectra of both solution and solid-state NMR. For more details on the seminar please see the flyer below.

Guide: Connecting remotely to NMR 800CP

As a convenience for the users of NMR 800CP, users can remotely monitor the progress of their experiments using VNC servers. Users have to manually start the X11VNC server and access using VNC viewers (like RealVNC viewer). Instructions on this process is available here: http://bionmrcore.umich.edu/wp-content/uploads/2018/11/Accessing-the-Bruker-800CP-machine-in-Chem-1047-using-VPN.pdf

NMR Technique Highlight: BEST and SOFAST NMR for assigning His & Tyr side-chains

In the following paper, the authors present a NMR technique that uses time-efficient resonance assignment of histidine and tyrosine side chains in uniformly 13C/15N-labeled proteins. The use of band-selective 13C pulses allows to deal with linear chains of coupled spins, thus avoiding signal loss that occurs in branched spin systems during coherence transfer. Details of the paper can be found in the link below:

Christou NE, Brutscher B, BEST and SOFAST experiments for resonance assignment of histidine and tyrosine side chains in 13C/15N labeled proteins (2018) J. Biomol NMR doi: 10.1007/s10858-018-0216-z Link: https://link.springer.com/article/10.1007/s10858-018-0216-z

NMR Webinars by Bruker

Bruker has various webinars on advanced NMR techniques and technologies.

Link: https://www.bruker.com/service/education-training/webinars/nmr-webinars.html

NMR Conferences

Here are a few conferences (deadlines are fast approaching) that current BioNMR users will find useful:

  1. Biophysical Society 63nd Annual Meeting (March 2-6, 2019) at Baltimore, Maryland Link: http://www.biophysics.org/2019meeting
  2.  PANIC 2019 Practical Applications of NMR in Industry Conference (March 3-7, 2019) at Hilton Head, South Carolina Link: http://www.panicnmr.com/
  3. 60th Experimental Nuclear Magnetic Resonance Conference (April 7 – 12, 2019) at Asilomar Conference Center, Pacific Grove, California
  4. Computational Aspects of Biomolecular NMR – Gordon Research Seminar (June 8-9, 2019) at Les Diablerets, Switzerland Link: https://www.grc.org/computational-aspects-of-biomolecular-nmr-grs-conference/2019/
  5. ISMAR 2019 21st International Society of Magnetic Resonance Conference joint with EUROMAR 2019 (August 25-30, 2019) at Berlin, Germany Link: http://www.ismar2019.org/

NMRFAM-Sparky tutorial videos

Sparky is the most popular NMR analysis tool for biomolecules for more than a decade. NMRFAM has taken over the original Sparky from UCSF for the continuous development to implement advances in biomolecular NMR field. This software is very useful for biological NMR community for NMR resonance assignment, structure prediction, semi-automatic structure calculation, etc. For details on the updated NMRFAM-Sparky software can be found here: https://nmrfam.wisc.edu/nmrfam-sparky-distribution/

There is a YouTube playlist of video tutorials on NMRFAM-Sparky software:

NMR Staff

Debashish Sahu, Ph. D.
Director, Biomolecular NMR Research Lab
LSA/LSI Core Facility 
University of Michigan
Chemistry Building Room # 4015
930 N University Ave, Ann Arbor MI 48109

Email: debsahu@umich.edu
Phone: 734-647-3872


Wendy Feng, Ph. D.
Senior Lab Specialist
BioNMR Core Facility

University of Michigan
Life Sciences Institute # 3214
210 Washtenaw Ave, Ann Arbor MI 48109
Email: wendyfen@umich.edu
Phone: 734-615-5516

Emily Scott, Ph.D.
Professor, Medicinal Chemistry/Pharmacology/Biophysics
Faculty Director, BioNMR Core Lab
University of Michigan
428 Church Street
Ann Arbor, MI 48109-1065
Email: scottee@med.umich.edu
Phone:  734-764-3530
Lab webpage:  http://scottlab.info

Cathy Andrews
Director of Operations
BioNMR Core Lab
University of Michigan
Life Sciences Institute # 3119
210 Washtenaw Ave, Ann Arbor MI 48109 

Email: cathyand@umich.edu
Phone:  734-763-1200

Interactive graphs of Aliphatic Carbon and Proton Chemical shifts

In order to assist with chemical shift assignments of proteins, here are two plots of aliphatic chemical shifts based on BMRB data as of 10/17/2018.

For assignments of Cα and Cβ present in proteins, we usually run HNCACB and CBCA(CO)NH. Some residues such as Gly, Leu, Ala, Thr, Ser etc can be used as anchor points for starting assignments due to their unique distribution of aliphatic carbon chemical shift as shown below. Once can use this interactive map of chemical shifts below for chemical shift assignment. 

A similar graph has been generated for assignments of aliphatic protons below. HCCH-TOCSY and H(CCCO)NH-TOCSY experiments give rise to chemical shifts of aliphatic protons, where this interactive distribution of chemical shift can be used for assignment purposes.