Annual Meeting

Seeking new techniques to track
protein breakdown

Jana Zecha named MCP early-career investigator
Alyson Smith
March 01, 2019

Jana Zecha has developed techniques that will help researchers learn how protein modifications can affect their stability.Cells are protein factories, constantly making new proteins and breaking down damaged or unnecessary ones. Cells must regulate these processes tightly for thousands of proteins to support cellular function, and Jana Zecha has developed a new technique to monitor this protein turnover.

Jana Zecha

During her early biology courses in Burghausen, a small town in Bavaria, Zecha became curious about how single molecules work together to produce a functioning organism. She earned a bachelor’s degree at the Technical University of Munich, completing a thesis project on gene expression in gestational diabetes. She became interested in technologies that scientists could harness to investigate the molecular bases of disease.

Zecha remained in Munich to work in Bernhard Küster’s group, earning a master’s degree and then beginning her Ph.D. research, studying how protein modifications determine their breakdown rates at a cell-wide level. Her project built on earlier work in the Küster lab that suggested established methods had difficulty tracking modified proteins.

Using the classical approaches for the measurement of cellular protein turnover,” Zecha said, “many important aspects of cell biology have so far been overlooked or remained ‘invisible.’”

After developing new techniques and data analysis approaches, she could track breakdown and production of thousands of modified proteins over time. Her work has laid the foundation for future investigations into how protein modifications can affect their stability.

Zecha enjoys teaching young scientists. She has mentored undergraduate researchers in the Küster lab and has taught courses in Munich and Taiwan.

“Although teaching is, of course, always lots of work,” she said, “for me it is also great fun and a pleasure to pass on my enthusiasm for science and guide and help students to recognize and develop their potential.”

Zecha is in the final stage of her Ph.D. thesis work in Bernhard Küster’s lab.

Tagging and tracking modified proteins

Multiple versions of the same protein can arise from a single gene, either through alternative splicing of messenger RNA or through chemical modifications of the final protein product. These modifications can change the protein’s life span, affecting how long it can carry out its function.

Jana Zecha and her colleagues developed a strategy to measure the life spans of thousands of proteins simultaneously. They fed cells amino acids made with heavier carbon and nitrogen isotopes. As the cells digested old proteins and produced new ones, more and more proteins incorporated heavy amino acids. They combined this system with a tagging method to track protein replacement over time.

The protein lives they measured spanned several orders of magnitude; some were broken down and replaced in minutes, while others lasted weeks. Because their data set captured thousands of proteins, the researchers could detect relationships between protein life span and protein abundance, chemical composition and cellular location. They also detected new relationships between modifications and life span.

“Our study has broad implications for basic as well as pharmaceutical research, since many neurodegenerative, age-related and cancer diseases are associated with altered protein life spans,” Zecha said.

The researchers plan to leverage their new tools to connect protein life span with cancer drug efficacy and side effects.

Alyson Smith

Alyson Smith is a recent Ph.D. graduate from Scripps Research in La Jolla, California. Follow her on Twitter.

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in People

People highlights or most popular articles

Protein society awards; Parise named dean; remembering Bud Patterson
Member News

Protein society awards; Parise named dean; remembering Bud Patterson

March 30, 2020

Awards, honors, promotions and more. Find out what's going on in the lives of ASBMB members.

Stanley Cohen (1922 – 2020)
Retrospective

Stanley Cohen (1922 – 2020)

March 23, 2020

Laura Furge remembers a Nobel laureate who discovered epidermal growth factor and its receptor, work that has allowed generations of biochemists to study the pathways that allow cells to respond to external events.

Chu wins educator award; Cech honored; remembering Holmgren
Member News

Chu wins educator award; Cech honored; remembering Holmgren

March 23, 2020

Awards, promotions and more. Find out what's going on in the lives of ASBMB members.

The best of two worlds
Journal News

The best of two worlds

March 19, 2020

Cecil Pickett’s research career spanned several decades and led to pivotal findings on oxidative stress responses and key breakthroughs in drug discovery.

Ron Kaback (1936 – 2019)
Retrospective

Ron Kaback (1936 – 2019)

March 16, 2020

Gary Rudnick remembers his friend and mentor, a biochemist who combined a deep love of science with a prankish sense of humor.

Patton–Vogt to lead department; Wiley Prize for Rosen; and more
Member News

Patton–Vogt to lead department; Wiley Prize for Rosen; and more

March 16, 2020

Awards, promotions and more. Find out what's going on in the lives of ASBMB members.