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Volume 8, Issue 4 | Fall 2023

Science Feature

Nicholas Cina, a fourth-year graduate student in the Klug Lab, discusses his research interests.

My current work as a fourth-year graduate student in Candice Klug’s lab involves the structural investigation of proteins required for lipopolysaccharide (LPS) shuttling from the inner membrane to the outer membrane of Gram-negative bacteria. LPS provides a physiochemical barrier against a variety of antimicrobial compounds, and proper localization of LPS to the outer membrane is essential for bacterial viability. Therefore, structural investigation of the LPS transport (Lpt) system will lay the groundwork for targeted approaches to inhibit or hinder outer membrane biogenesis.

I specifically study the inner membrane component of the Lpt system, LptB2FG. This protein complex is an ATP binding cassette transporter and is the driving force of the Lpt system, extracting LPS from the inner membrane and providing energy to push the glycolipid through the rest of the Lpt system.

The current model of LptB2FGC-mediated expulsion of LPS from the inner membrane lacks several important steps that are likely critical for transport. LptB2FGC undergoes drastic conformational rearrangement of the LptF and LptG transmembrane helices during LPS transport. The LptC helix has been reported to regulate transport; however, the conformational dynamics of the LptC helix during LPS transport have yet to be characterized. I have recently defended my dissertation proposal, which outlines a set of experiments to uncover the various conformational states of the LptC helix. Our lab primarily utilizes EPR (electron paramagnetic resonance) techniques to achieve this. Continuous-wave EPR can illuminate the local protein environment at specific regions of the LptC helix, and DEER (double electron–electron resonance) spectroscopy can determine if the helix displaces entirely from the complex. The completion of my proposal will shed light on this existing knowledge gap by providing important information on conformational states and dynamics of the complex not completely resolved by the published structures. In turn, these structural experiments will support efforts to develop targeted approaches to specifically hinder or inhibit LPS transport, thereby increasing susceptibility of the bacterium to antibiotic treatment in injections.

The Importance of Collaborating Across Disciplines

By Balaraman Kalyanaraman, PhD

In winter of 2021, I penned the article, "Reimagine: It's Easy if You Try," for the Kern Institute's Transformational Times. One section of the article—"A great example of reimagining"—focuses on biochemist Katalin Karikó, PhD, who laid the foundation for the messenger RNA therapeutics used to develop the COVID-19 vaccine. Her research was funded only after she struck up a collaboration with immunologist Drew Weissman, MD. Together, they had the idea to modify the structure of an RNA nucleoside as a means to design therapeutic RNAs.

In 2023, Dr. Karikó and Dr. Weissman received the Nobel Prize in Physiology or Medicine “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.”

Dr. Karikó's work speaks to the importance of perseverance and determination in one's research. Further, it is an excellent example of why basic scientists (i.e., in the fields of chemistry, biochemistry, and biophysics) should collaborate with scientists in other disciplines with clear translational potential.

Alumni Q&A

Learn about the diverse career paths our alumni have pursued after graduating from the Biophysics Graduate Program.

Zhan Xu, PhD, Research Scientist at MD Anderson Cancer Center

As a graduate student at MCW, Zhan Xu studied under the mentorship of Shi-Jiang Li, PhD, professor in the Department of Biophysics. Zhan received his PhD in 2018 with his dissertation titled "MR Pulse Sequence Design of the Intra-Shot Adapted Keyhole (ISAK) Acquisition Method and Its Applications in Functional MRI." Today, Zhan is a research scientist at the MD Anderson Cancer Center.

Zhan Xu and daughter golfing

Zhan "teaching his daughter to let the ball fly!"

Q: What inspired you to pursue a career in science? 

A: My mentor in graduate school was Dr. Shi-Jiang Li. He set a great example for balancing intellectual challenges, long-term career planning, and personal life. His dedication to daily academic life encouraged me to pursue my goals with confidence.

Q: Since completing your PhD in Biophysics in 2018, share with us your career progression to your current role as a research scientist at MD Anderson Cancer Center.

A: I consider myself fortunate to have had the opportunity to enhance my strengths and capabilities in various aspects of my field while at MD Anderson (MDA). The organization provided me with the freedom to choose and focus on specialties that aligned with my interests. Additionally, MDA encouraged us to explore external opportunities and foster communication with the industry to stay abreast of its rapid developments.

Q: Tell us about your major responsibilities, and the types of projects, committee service, or other activities you might work on in a typical week.

A: I am a full-time researcher specializing in the development of machine-learning models for tumor diagnosis and prediction applications.

Q: What aspect of your current job do you find most rewarding, and why?

A: Having instant feedback and maintaining frequent communication with physicians. Without these elements, it becomes very easy to fall into the pitfall of focusing solely on technology and losing sight of the primary goal: facilitating applications for disease management. My responsibility now extends beyond demonstrating personal intellect; it is to provide physicians with efficient and practical solutions.

Q: What advice do you wish you had been given as a graduate student?

A: First, always ask yourself why you have to do the current work and consider the bigger picture it could lead to. Second, regularly update your resume and schedule several interviews with the industry every summer to assess your real-world capabilities.

Q: How do you continue learning and growing as a professional? What are some of your habits aside from reading/listening?

A: This is the challenging part: I have to make sacrifices and give up certain choices to acquire truly valuable skills. It is often more difficult to reduce rather than add things in one's personal life. One helpful strategy I've discovered is explaining what I do to my kids or parents; discussing your work with an outsider is an excellent way to identify professional weaknesses and mirror areas for improvement.

Seminar Series

Our Fall 2023 Biophysics Graduate Seminar Series takes place most Fridays throughout the semester, from 10:00 a.m. to 11 a.m., in MFRC 2063 (except as otherwise noted). For details, please visit the Biophysics Events page.

Sept. 1 | Wei Liu, PhD (MCW)
Biophysical characterizations of membrane protein in structural biology

Sept. 8 | Nicholas Cina (MCW)
Residues within the LptC transmembrane helix are critical for Escherichia coli LptB2FG ATPase regulation

Sept. 15 | Brooke Greiner (MCW)
Applying connectome predictive modeling to attentional control performance

Sept. 29 | Julian Grosskopf (MCW)
Exploring the conformational dynamics of β2-AR through interactions with negatively charged lipid headgroups

Oct. 6 | Kyle Johnson (MCW)
Technology development for pre-clinical MRI at 9.4T

Oct. 13 | Jarett Wilcoxen, PhD (UW-Milwaukee)
Understanding how nature tunes the molybdopterin cofactor

Oct. 20 | Dylan Murray, PhD (University of California, Davis )
Solid state NMR characterization of low complexity protein sequence assembly mechanisms

Oct. 27 | Carol Williams, PhD (MCW)
Strategies to control malignancy by regulating the localization of small GTPases in cancer cells

Nov. 10 | Stefan Stoll, PhD (University of Washington)
Mapping protein conformational changes using EPR/DEER spectroscopy

Nov. 17 | Allison Ebert, PhD (MCW)
Using stem cells to model neurodevelopment and neurodegeneration

Dec. 1 | Savannah Duenweg (MCW)
Non-invasive tracking of prostate cancer risk assessment using radio-pathomic mapping

Dec. 8 | Wai-Meng Kwok, PhD (MCW)
Diverse roles of mitochondrial VDAC1 in disease: a molecular conundrum

Dec. 15 | Jim Hokanson, PhD (Marquette University & MCW)
What’s the role for brain imaging in advancing urological care?

Department News

Welcome

  • Nikolai Mickevicius (assistant professor)
  • Rajlaxmi Panigrahi (postdoc, Marassi lab)
  • Akansha Sharma (postdoc, Sidabras lab)
 

Congratulations

  • Nicholas Cina & Candice Klug published an article in Applied Magnetic Resonance as part of a special issue dedicated to Wayne Hubbell on the occasion of his 80th birthday.
  • Savannah Duenweg published an article in the Journal of Pathology Informatics. 
  • Savannah Duenweg & Biprojit Nath published an article in Cancers.
  • Bryna Goeckner published an article in Archives of Clinical Neuropsychology.
  • Balaraman Kalyanaraman was conferred the title of Doctor Honoris Causa by the University of Aix-Marseille, France.
  • Balaraman Kalyanaraman & Gang Cheng published an article in Expert Opinions in Therapeutic Targets.
  • Shi-Jiang Li published an article in Frontiers in Neuroscience.
  • Francesca Marassi published an article in Biochemistry. An image from the article was selected for the journal's cover.
  • Francesca Marassi was named MCW Cancer Center associate director of shared resources.
  • Kathleen Schmainda published an article in Nature Communications.
  • Katie Schultz & Candice Klug published an article in the Journal of Molecular Biology.
  • Jason Sidabras published an article in Radiation Protection Dosimetry.
  • Karol Subczynski published an article in Antioxidants.
  • Jacek Zielonka published an article in Antioxidants (which was selected as the journal's cover story) and an article in Chemical Research in Toxicology.
 

Biophysics Participated in the LLS Light the Night Event

The MCW Department of Microbiology & Immunology coordinated an MCW team for the Leukemia & Lymphoma Society's Light the Night event on Oct. 5, 2023, at Henry Maier Festival Park; members of Biophysics jointed the team. The MCW team, named CAR-T PAR-T after a form of cancer treatment, raised $11,300—the third-highest amount raised in the community and school teams category.

Light the Night logo

If you wish to contribute to CAR-T PAR-T's fundraiser to help cure cancer, donations are still being accepted.

MCW CAR-T PAR-T Team

MCW's CAR-T PAR-T team at the 2023 Light the Night event.

Shoutout to Kathleen Schmainda & ECOG-ACRIN Clinical Trial Team

A recent MCW Cancer Center Clinical Trials newsletter article featured the ECOG-ACRIN EAF151 trial, which is led nationally by Kathleen Schmainda. The clinical trial has reached accrual and is now entering the analysis stage.

Well-Behaved Women Seldom Make History

At MCW's 2023 Women’s Full Professor Recognition Ceremony, Francesca Marassi received lapel pin #252, which signifies the order in which her MCW professorship was achieved. The theme of the event was "well-behaved women seldom make history."

Faculty Awards and Honors

The 2023 MCW Faculty Awards and Honors celebration honored Francesca Marassi as a new chair and eminent scholar. Additionally, Jeannette Vasquez Vivar and Neil Hogg were honored for their 25 years and 30 years of service, respectively.

Recipe

Roasted Delicata Squash

Serves 2–4

Recipe by 101 Cookbooks

Ingredients

1/2 pound small fingerling potatoes, washed and dried
3/4 pound delicata squash
1/4 cup extra virgin olive oil
scant 1/4 cup white miso
scant 1 tablespoon harissa paste
3 tablespoons freshly squeezed lemon juice
1 1/2 ounce kale, de-stemmed and finely chopped
4 radishes, very thinly sliced
1 1/2 ounces Marcona almonds, toasted pepitas, or other toasted nuts

101 Cookbooks: Roasted Delicata Squash

Instructions

  1. Preheat the oven to 400°F degrees. If the potatoes aren't tiny, slice them into pieces no larger than your thumb. Cut the delicata squash in half length-wise, and use a spoon to clear out all the seeds. Cut into 1/2-inch wide half-moons. You can leave the peel on these squash.
  2. In a small bowl whisk together olive oil, miso, harissa. Place the potatoes and squash in a large bowl with 1/3 cup of the miso-harissa oil. Use your hands to toss well, then turn everything out onto a baking sheet. Bake until everything is cooked through and browned, about 25-30 minutes. Toss once or twice along the way after things start to brown a bit. Keep an eye on things though, you can go from browned to burned in a flash.
  3. In the meantime, whisk the lemon juice into the remaining miso-harissa oil. Adjust taste as needed: It should be intensely flavorful, but if yours is too spicy or salty, you can dilute it with a bit more olive oil or lemon juice. Stir the kale into the leftover dressing and set aside.
  4. Place the warm roasted vegetables in a bowl and toss with the kale mixture, radishes, and almonds.

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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