Volume 10, Issue 2 | Spring 2025

Science Feature

From Structure to Mechanism: Solving a Longstanding Puzzle in Cellular Energy Metabolism

By Vanessa Leone, PhD

We recently published a study that provides new insight into a fundamental step in cellular metabolism. Pyruvate, the end product of glycolysis, must be transported into mitochondria to fuel oxidative phosphorylation, enabling the production of roughly 15 times more ATP than anaerobic metabolism. This critical step is mediated by the mitochondrial pyruvate carrier (MPC), a protein complex identified just over a decade ago. Despite its central role, the structure and mechanism of the MPC have remained elusive.

In collaboration with Edmund Kunji’s lab (MRC Mitochondrial Biology Unit, University of Cambridge, UK), we determined the first high-resolution structure of the MPC using cryo-electron microscopy. This revealed the atomic architecture of the complex and its binding interactions with several small-molecule inhibitors, offering a structural framework for drug development.

While cryo-EM provides detailed structural snapshots, understanding the dynamic process of transport requires a complementary approach. We used AlphaFold to model the full conformational cycle of the MPC, allowing us to explore how it changes shape to carry out transport. Strikingly, several predicted intermediate states aligned closely with our cryo-EM data, highlighting the power of AI-based tools to illuminate protein dynamics that are challenging to capture experimentally.

These structural and computational insights help resolve a metabolic question that has persisted for over 50 years. Given the MPC’s involvement in conditions including diabetes, fatty liver disease, neurodegeneration, cancer, and hair loss, this work opens new avenues for the rational design of targeted therapeutics.

MPC in outward-open, closed, and inward-open states.

Biophysics Presents

Second Annual James S. Hyde, PhD, Memorial Lecture

Guest Lecturer: David D. Thomas, PhD

Please join us for the second annual James S. Hyde, PhD, Memorial Lecture, which will honor the remarkable legacy of Dr. Hyde, a world-renowned expert in electron paramagnetic resonance spectroscopy instrumentation, a pioneer in functional magnetic resonance imaging, and a leading authority on brain connectivity.

The memorial lecture will be held on Mon., May 19, from 10–11:30 a.m. in the MCW Alumni Center. Guest lecturer David D. Thomas, PhD, Professor; Dietrich Chair; and Director, Minnesota Muscle Training Program, University of Minnesota, will present his talk, "Spectroscopic Probes of Protein Structural Dynamics, Thanks to Jim Hyde!"

See the event page for additional information.

Happy Retirement, Tim!

Tim Thelaner will retire after 25 years of service to the Department of Biophysics.

Tim Thelaner, Engineer II in the Department of Biophysics, will retire on August 1, 2025. Tim’s experience and support have been instrumental in the success of the Department over the past 25 years, and his knowledge of the Department's inner workings will be missed dearly.

Tim began his career at MCW as an engineering technician in the Department of Biophysics, developing new research equipment for human and animal MRI scanners. He then began supporting the development and maintenance of custom-built EPR spectrometer equipment and accessories in the National Biomedical EPR Center.

Tim's hard-working ethics, knowledge, collegiality, and professionalism are matched only by his generosity and congeniality.

In his retirement, Tim looks forward to pursing his hobbies (biking, travel, woodworking, home projects), and enjoying time with his two granddaughters.

We are endlessly grateful for Tim’s fantastic service to the Department of Biophysics. We wish him all the best in retirement.

Graduate Student Q&A

Learn about the students in our Biophysics Graduate Program.

Bryna Goeckner

Program: Neuroscience Doctoral Program
Mentor: Timothy B. Meier, PhD
Year Entered MCW: 2021

Background: I earned my BS in chemical engineering at the University of Illinois and worked in the power industry on environmental controls and reutilization of coal combustion byproducts.

I then went to Cardinal Stritch University for my MA in teaching and taught high school science and math. Wanting something different but still connected to science, I decided to try research and applied to graduate school.

I grew up in the Milwaukee area and my family still lives nearby. As a mom to two teenagers, I’m always busy keeping up with them and their many interests.

Research Interests: I study concussion in female athletes, focusing on the role of hormones and hormonal contraception in their outcomes.

Future Plans: I would love to work in the advocacy/policy realm of supporting women-specific research to provide more individualized healthcare for everyone. Toward that goal, I recently completed the Wisconsin Women’s Network Policy Institute program, which allowed me to gain related skills and experience working with a team remotely and in Madison. I am currently working on arranging a similar “internship” experience to round out the rest of my time here at MCW—while I finish my research, of course.

Fun Fact: I was an only child for 13 years, but now have nine siblings of one sort or another.

Bryna Goeckner receiving her certificate of completion from the Wisconsin Women's Network Policy Institute.

Biophysics Alumni: Where Are They Now?

Rasmus Birn, PhD

Title & Institution: Associate Professor, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health
Location: Madison, WI
Year Graduated MCW: 2000
Mentor: Robert Cox, PhD

Seung-Yi Lee, PhD

Title & Institution: Advanced Workflow Specialist – Widefield, Leica Microsystems
Location: San Francisco, CA
Year Graduated MCW: 2022
Mentor: Matthew D. Budde, PhD

Alexander M. Puckett, PhD

Title & Institution: University of Technology Sydney, Graduate School of Health
Location: Sydney, Australia
Year Graduated MCW: 2013
Mentor: Ted DeYoe, PhD

Benjamin Stengel, PhD

Title & Institution: Project Manager, Epic
Location: Melbourne, Australia
Year Graduated MCW: 2012
Mentor: Jeffrey R. Binder, MD

Department News

Welcome

Sandra Byju (Postdoctoral Researcher, Marinelli lab)
Meghan Byrne (Administrative Associate)
Carlos Herrada (Graduate Student, Leone lab)
Callie Koenig (Research Technologist I, Klug lab)
Tyler Trask (Graduate Student, Marinelli lab)

Farewell

Emmanuel Barbosa (Postdoctoral Researcher, Marinelli lab)
Shannon Gustavson (Administrative Associate)
Steven Traeger (Research Technologist I, Vasquez Vivar lab)

Congratulations

Patrick Brennan & Mike Lerch published an article in Science Advances.
Nicholas Cina & Candice Klug published an article in Protein Science.
Bryna Goeckner published an article in Medicine & Science in Sports & Exercise.
Aleksandra Grzelakowska & Jacek Zielonka published an article in Analytical Chemistry.
Balaraman Kalyanaraman published an article in International Journal of Molecular Sciences.
Vanessa Leone published an article in Science Advances and was featured in the April 15th issue of the MCW Cancer Center's The Cancer Code.
Vanessa Leone & Fabrizio Marinelli published an article in The Journal of Chemical Physics.
Rajlaxmi Panigrahi published an article in ACS Chemical Neuroscience.
Karol Subczynski published a letter to the editor in Experimental Eye Research.
Gopinath Tata, Alyssa Kraft, Kyungsoo Shin, Nick Wood, & Francesca Marassi published an article in Journal of Biomolecular NMR.
An article by Steven Traeger, James Woodcock, and Jeannette Vasquez Vivar, "Tetrahydrobiopterin as a rheostat of cell resistance to oxidant injury," was featured in Chemicals & Chemistry Daily.
Aleksandra Winiarz received a 2025 Graduate Student Travel Award from the MCW Graduate Student Association.
Aleksandra Winiarz & Biprojit Nath published an article in Frontiers in Oncology.
Casey Zoss received a 2025 Graduate Student Travel Award from the MCW Graduate Student Association.

Research Day 2025

These Biophysics personnel participated in the Office of Research's Research Day 2025 poster sessions:

Benjamin Chao - "SOX-2 expression across whole brain slices identifies tumor well
beyond contrast enhancement and FLAIR hyperintense regions in
glioblastoma patients"
Kesaban Sankar Roy Choudhuri - "Elucidating the complex interaction between Parkin and its substrate involved in Parkinson’s disease pathogenesis"
Biprojit Nath - "Tumor Probability Map-Derived Peak Separation Index as a Prognostic
Marker in Glioblastoma: Insights into Tumor-Edema Demarcation and
Survival"
Alex Skitowski - "Using Machine Learning Models to Predict Depression after Resective
Epilepsy Surgery"
Aleksandra Winiarz - "SOX2 for detecting the extent of true tumor invasion at autopsy in patients with MRI close to death"

Featured Pet

Name: Zuko Grosskopf
Breed: German shepherd
Age: 4 years
Likes: Frisbees
Dislikes: Snow shovels
Guardian: Julian Grosskopf
Origin story: My family has had shepherds my whole life, and I wanted one of my own at some point. During medical school, I knew I would be working from home for nearly 6–8 months studying for boards and thought, "What a great time to get a puppy!" So, I looked for a breeder and ended up finding Zuko! He is extremely patient, gentle, great at listening, and is a great companion. He has been such a blessing to us, and we're fortunate to have a dog like him!

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, events, photos, a photo of your pet? Send it to Lydia.

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