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Volume 8, Issue 1 | Winter 2023

Science Feature

New Spins in the Department of Biophysics

Gopinath Tata, PhD, assistant professor of biophysics, discusses his research interests.

I am excited to have recently joined the solid-state nuclear magnetic resonance (NMR) team in the Department of Biophysics. Solid-state NMR spectroscopy is a powerful technique for analyzing structure and dynamics of biomolecular systems such as proteins, irrespective of their molecular size. However, low sensitivity and resolution are limiting factors for scaling the technology to large biomolecular systems. In solid or semi-solid-samples, nuclear spins are coupled via strong dipolar couplings, leading to local polarization pools or undetectable spin operators that are often discarded in the conventional solid-state NMR experiments. However, it is possible to manipulate the spin polarization via radio frequency pulses in such a way to recycle or reuse (instead of discarding) the polarization, leading to cost-effective data acquisition. In this direction, our research focuses on developing high-throughput multi-dimensional data acquisition methods to push the boundaries of solid-state NMR applications to large biomolecular systems. These developments will have further impact when combined with new technologies such as ultra-fast magic angle spinning and multi-receiver solid-state NMR.

Gopinath Tata, PhD

The past few years have witnessed several breakthroughs in protein structural biology using solid-state NMR. These include new sample preparation methods, dynamic nuclear polarization, ultra‐high‐field magnets, and more recently cryogenic probes for increased sensitivity. However, given the spectral complexity of large protein systems, obtaining high-resolution atomic information from crowded solid-state NMR spectra can be challenging. To address this problem, in parallel with experimental and technological advancements, computational approaches are being developed at a rapid pace. To that end, the Marassi lab has developed computational tools that facilitate analysis of the NMR data and high-resolution structure calculations. We are thrilled to have excellent resources at MCW's Research Computing Center and are thankful to their staff for helping us kick off our protein simulations. 

NMR and electron paramagnetic resonance (EPR) are known as the key branches of magnetic resonance spectroscopy. While NMR experiments measure inter-atomic distances of few angstroms, EPR enables long-range nanometer distance measurements. Furthermore, solid-state NMR and EPR can be combined in new experiments, such as dynamic nuclear polarization. This approach has novel applications in overcoming the low sensitivity of solid-state NMR experiments with a wide variety of uses, ranging from materials to biomolecules and cellular extracts. We look forward to collaborating with the EPR experts in the Department of Biophysics to pursue a combined magnetic resonance approach in method developments and applications to large protein complexes.

Seminar Series

The Spring 2023 Biophysics Seminar Series takes place most Fridays throughout the semester, from 10 a.m. to 11 a.m., via Zoom. Additional details about these events are available on the Biophysics Events page.

Jan. 27 | Thota Ganesh, PhD (Emory School of Medicine)
Prostaglandin-E2 receptor EP2 drives neuroinflammation and cognitive deficits in the models of epilepsy and Alzheimer’s disease

Feb. 3 | G. Marius Clore, MD, PhD, DSc (Hon), FRS (NIDDK, National Institutes 
of Health)

Probing transient, pre-nucleation oligomerization of huntingtin by NMR relaxation-based methods

Feb. 10 | Bharat Biswal, PhD (New Jersey Institute of Technology)
Toward brain connectomics: Examining brain connectivity during rest and movie watching 

Feb. 17 | Kevin Bennett, PhD (Washington University School of Medicine)
Mapping whole kidney structure and function at the scale of the individual nephron using MRI    

Feb. 24 | R. Scott Prosser, PhD (University of Toronto Mississauga)
Understanding receptor pharmacology - NMR-inspired studies of GPCR activation and connections 

March 3 | Shella Keilholz, PhD (Georgia 
Tech and Emory University
)
The organization of intrinsic brain activity

March 10 | Clemens Glaubitz, PhD (Goethe University)
Solid-state NMR studies on LPS transporters

March 17 | James Pipe, PhD (Mayo Clinic)
Value, complexity, and Occam’s MRI

March 31 | Que Van, PhD (Leidos Biomedical Research, Inc.)
How does the small GTPase KRAS recruits and activates RAF kinase at the plasma membrane?

April 7 | Ruma Banerjee, PhD (University of Michigan Medical School)
Coordination-linked redox chemistry choreography for metal trafficking

April 21 | Laxman Mainali, PhD (Boise State University)
Cholesterol inhibits alpha-crystallin binding to membranes and protects against cataract formation: EPR and AFM studies

April 28 | Aurora Martinez, PhD (University of Bergen)
Structural and regulatory basis for pharmacological modulation of dopamine synthesis and transport

May 5 | Ana Denicola, PhD (University of Uruguay)
Tryptophan fluorescence of peroxiredoxins to study catalysis and oligomerization

A Look at the Biophysics Graduate Program

In previous issues of Biophysics News, we have highlighted alumni of the Biophysics Graduate Program. In this issue, we wanted to step back and shine a light on the program itself.

The MCW School of Graduate Studies (formerly known as the MCW Graduate School of Biomedical Sciences) was officially established in 1995, but the Biophysics Graduate Program had operated in an informal capacity (i.e., before Biophysics obtained department status) since the 1970s. In 1982, Carol Popp Weingarten, MD, PhD (mentor: James S. Hyde), was the first graduate from what would become the Biophysics Graduate Program. In August 2022, Samuel Bobholz, PhD (mentor: Peter S. LaViolette), was the 110th graduate of the program.

The Biophysics Graduate Program is directed by Candice Klug, PhD, James S. Hyde Professor of Biophysics, and an alumna of the program herself. Twenty-two graduate faculty, from the Departments of Anesthesiology, Biomedical Engineering, Biophysics, Neurology, Neurosurgery, Ophthalmology, Radiology, and Radiation Oncology, are available to mentor students in the program.

The graduate program features two primary research areas: Magnetic Resonance Imaging and Molecular Biophysics. Within each track, students are offered hands-on training in a variety of research topics, ranging from application of new technologies in biological problem-solving to cognitive neuroscience to structural and functional dynamics of proteins.

The Biophysics Graduate Program strives to provide a curriculum that enables students to acquire basic knowledge for biomedical research; develop critical thinking, integrative reasoning, and technical skills for research; and obtain the oral and written communication skills required for research and teaching responsibilities. The curriculum provides a comprehensive understanding of magnetic resonance techniques in biophysics and molecular biophysics and is sufficiently flexible to meet the interests and needs of individual trainees.

Biophysics Graduate Program
 

Department News

Welcome

  • Laura Borst (Administrative Coordinator)
  • Agnes Keszler (Research Scientist I, Hogg lab)
  • Biprojit Nath (Graduate Student, mentor: Peter LaViolette)
 

Congratulations

  • William Antholine published an article in Biochemistry.
  • Patrick Brennan (mentor: Mike Lerch) received an F31 grant, titled Structural basis for regulation of beta2 adrenergic receptor signaling by the dynamic post-translational modification S-palmitoylation.
  • Savannah Duenweg published an article in PeerJ Computer Science.
  • Bryna Goeckner published an article in Archives of Clinical Neuropsychology.
  • Francesca Marassi received MCW's Eminent Scholar designation, which is the highest recognition of academic excellence for faculty members at MCW.
  • Briana Meyer and Seung-Yi Lee published an article in the Journal of Neurotrauma.
  • Melissa Prah and Kathleen Schmainda published an article in Frontiers in Oncology.
  • Lydia Washechek was promoted to grants operations coordinator.
Mike Lerch, PhD (left), & Patrick Brennan (right)

Mike Lerch, PhD, and Patrick Brennan celebrate Patrick's F31 grant.

 

International NIAID RNCP/IRSN Collaboration

Jason Sidabras, PhD, recently attended a reinvigorated kickoff symposium between the National Institute of Allergy and Infectious Diseases (NIAID) Radiation and Nuclear Countermeasures Program (RNCP) and the Institute for Radiological Protection and Nuclear Safety (IRSN) in Paris, France. The symposium was joined by a select few researchers from the United States to be paired with IRSN collaborators to provide new research and insights into radiation-induced cutaneous and gastrointestinal injuries. Dr. Sidabras was invited due to his experience in electron paramagnetic resonance (EPR) technology and its use for in vivo measurements of reactive oxygen species and ionizing radiation dosimetry. This collaboration opens future funding avenues and provides an international link with clinical and preclinical uses for EPR technology. 

MCW Graduate Research Poster Day

Biophysics Graduate Students Nick Cina (Klug lab), Savannah Duenweg (LaViolette lab), Bryna Goeckner (Meier lab), Briana Meyer (Budde lab), Margaret Stebbins (LaViolette lab rotation), and Aleks Winiarz (LaViolette lab) presented posters at MCW Graduate Research Poster Day. Here are a few photos of the event:

N. Hogg, K. Hilgendorf, N. Cina
B. Meyer
 

Job Openings: Faculty Positions, Postdoctoral Fellow, Research Associate I

We are seeking motivated, highly skilled, and creative individuals to join the Department of Biophysics. We have the following job openings:

  • Open-rank faculty appointment in the area of computational biophysics
  • Open-rank faculty appointment in the area of structural and chemical biology
    (This is an MCW Cancer Center position in partnership with the basic science departments.)
  • Postdoctoral fellow (EPR focus) in the Sidabras lab
  • Research associate I in the Marassi lab

Please visit our website for additional information: 
www.mcw.edu/departments/biophysics/careers

Recipe

Chicken Yassa

Serves four

Recipe from The New York Times

Ingredients

4 bone-in, skin-on chicken legs (2½ to 3 pounds)
4 scallions, trimmed, whites and greens finely chopped
2 tablespoons fresh thyme, finely chopped (or 2 teaspoons dried)
1 tablespoon white vinegar or apple cider vinegar
½ cup lime juice (from 3 or 4 limes), plus more as needed

Halloween Cookies by Simply Happy Foodie

4 tablespoons peanut, vegetable, or canola oil, plus more as needed
Kosher salt and black pepper
2 pounds yellow onions, halved, and sliced ½-inch thick
1 green bell pepper, halved, seeded, and cut into thin matchsticks
1 whole Scotch bonnet chile, poked with a fork (or 1 whole habanero chile, 1 to 2 minced jalapeños, or ½ to 1 teaspoon red-pepper flakes)
4 garlic cloves, finely chopped
4 teaspoons finely chopped fresh ginger
3 fresh or dried bay leaves
2 teaspoons Dijon mustard (optional)
Cooked rice or fonio, for serving

Directions

  1. In a large bowl, combine the chicken legs with the scallions, thyme, vinegar, ¼ cup lime juice, and 1 tablespoon oil. Marinate in the fridge for at least 2 hours or up to 24 hours.
  2. If using a grill or grill pan, heat it over high; if using a cast-iron skillet, heat 1 tablespoon oil over medium-high. (If cooking indoors, pat the chicken dry, discarding marinade, then brush the chicken lightly with oil.) Season the chicken all over with salt and pepper. Working in batches if necessary, grill or sear the chicken until browned on both sides, 6 or 7 minutes per side. Transfer the chicken to a plate.
  3. Meanwhile, in a large pot, heat the remaining 3 tablespoons oil over medium-high. When the oil is hot, add the onions in an even layer, season with salt and pepper, and let sear without stirring for 3 to 4 minutes. Using a wooden spoon, stir occasionally to prevent onions from burning at the bottom of the pot, and allow onions to cook until they start to caramelize and take on some color, 10 to 12 minutes.
  4. Add the bell pepper, chile, garlic, ginger, bay leaves, and mustard (if using), and continue stirring, adding 1 to 2 tablespoons of water as needed to avoid scorching at the bottom of the pot, another 5 minutes. Stir in another ¼ cup lime juice, and season with 1 tablespoon salt and 2 teaspoons pepper.
  5. Add the grilled chicken into the pot, tucking it under the onions, then top with 1 cup water. Stir well, smooth mixture gently into an even layer, cover, and simmer over medium until chicken is cooked through and tender, about 30 minutes.
  6. Season to taste and add more lime juice to taste, if desired. Serve chicken over rice or fonio, with onion mixture and sauce drizzled generously on top.

Biophysics News is a quarterly MCW departmental newsletter aimed at enhancing departmental engagement through information and good news sharing. Do you have information you’d like to share—news, a photo, a recipe? Send it to Lydia.

 

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