Cell biologist Julia von Blume studies the Golgi apparatus to decode protein sorting and trafficking
The Golgi apparatus, named after Italian biologist Camillo Golgi, is one of the most fascinating organelles in the cell. Commonly referred to as the post office of the cell, the organelle ensures the proper modification, packaging, and transport of proteins. Electron micrographs of the Golgi apparatus reveal a complex membrane network of cisternae and vesicles, a “beautiful chaos” able to conduct very elaborate tasks. Although the Golgi apparatus was first observed in 1898, it has kept most of its secrets to this day.
Professor Julia von Blume, a cell biologist at the Department of Cell Biology at Yale University, has dedicated her career to unlocking some of these secrets. She is particularly interested in the mode of action of protein sorting at the trans-Golgi network (TGN), the part of the organelle that faces the cell's plasma membrane. Julia and her team have made significant progress in understanding the molecular mechanisms that govern the sorting process, and their findings have important implications for our understanding of cellular function and disease.
Julia sat down with us right before the busy holiday season to reminisce about her scientific career.
Please tell us a bit about your origins. Where do you come from and what inspired you to become a scientist?
I come from southern Germany, a small town near Lake Constance named Ravensburg. I became very fascinated with science through my biology teacher in high school. He sparked my curiosity and excitement for biochemistry.
How did your educational path look like?
It wasn't straightforward at first. After finishing school, I explored various fields through internships. One was at a lawyer's office, but I quickly realized it wasn't for me. Another was at Ravensburger Spiele, the children’s game company, which turned out to be an incredible experience. At the time, they had an environmental office focused on managing chemicals and waste disposal from their manufacturing processes. I worked on an exciting project creating a database of all the company's chemicals. This role involved collaborating with multiple departments, and through these interactions, I discovered how much I enjoy this kind of work.
When did you decide you to start studying again?
At first, I hesitated to return to studying, worried that I might struggle with the intellectual demands and heavy workload of pursuing natural sciences. However, I ultimately decided to take the leap. The following year, I enrolled in the Biological Sciences Program at the University of Konstanz, specializing in Biochemistry, Biophysics, Biochemical Pharmacology, and Molecular Toxicology. For my diploma thesis (equivalent to a master’s thesis), I joined Werner Hofer's laboratory to study membrane biology and fusion using yeast as a model system. I found the straightforward genetic nature of yeast and the well-established tools for studying fundamental cell biology processes particularly compelling. However, for my Ph.D. thesis, I sought to explore mammalian cell biology, focusing on gaining foundational insights into cancer biology.
I interviewed at several laboratories, but Thomas Seufferlein's lab at the University of Ulm's medical school stood out as particularly intriguing. They had identified a protein kinase, protein kinase D, which is overexpressed in pancreatic cancer and plays multiple roles in the cell, depending on its cellular localization—for example, the nucleus, cytosol, Golgi apparatus, or plasma membrane. This protein kinase ultimately connected me to my postdoctoral lab.
During my Ph.D., Thomas Seufferlein invited Vivek Malhotra from the University of California, San Diego (UCSD), to spend a week with us in the lab at the University of Ulm. Vivek’s visit was incredibly inspiring—his groundbreaking ideas, deep knowledge, and remarkable creativity left a lasting impression on me. I became deeply interested in his work and eager to join his lab. During his visit, he invited me to spend time in his UCSD laboratory to gain firsthand insight into their research. I was thoroughly impressed by the lab’s creativity and rigorous research standards. Vivek offered me a postdoc position, but I hesitated initially due to the distance from my family. After some deliberation, I decided to take the opportunity, and it proved to be a truly fantastic experience.
I began the first part of my postdoc in San Diego before our laboratory relocated to the Centre for Genomic Regulation (CRG) in Barcelona. With the support of an Emmy Noether Fellowship from the German Research Foundation, I later moved to the Max Planck Institute of Biochemistry in Martinsried, Germany, where I established my first independent research lab as a Principal Investigator (PI).
Can you tell us about the research your laboratory conducts?
From the outset, I was deeply fascinated by the Golgi apparatus, particularly its role as a sorting and distribution center for intracellular proteins and lipids. During my postdoctoral studies, I became intrigued by the mechanisms underlying how secretory proteins are sorted at the trans-Golgi Network (TGN). The TGN functions like a molecular mail distribution center, assigning “addresses” to proteins and directing them to their proper destinations via vesicular transport carriers. These destinations include the cell surface or intracellular compartments such as endosomes, lysosomes, or secretory storage granules for regulated secretion, as well as the cell surface for constitutive secretion. A fundamental and still largely unanswered question is how soluble secreted proteins are selectively sorted into vesicular carriers and directed to their correct destinations. This question has become the central focus of my research.
In the late 1980s, Stuart Kornfeld and colleagues provided foundational mechanistic insights into soluble protein sorting in the TGN. They discovered that the mannose-6-phosphate receptor (M6P-R), a specific cargo receptor within the TGN membrane, recognizes phosphate groups on terminal mannose residues in the N-linked glycans of lysosomal enzymes. The M6P-R links hydrolases to the TGN membrane, enabling their packaging into clathrin-coated vesicles for transport to lysosomes. This discovery established the principle of receptor-ligand binding in protein sorting and sparked the hypothesis that similar mechanisms might govern the sorting of secretory proteins. However, no analogous modifications or conserved sorting motifs for secretory proteins nor their associated cargo receptors have been identified.
During my postdoctoral work, I identified the first cargo-receptor-independent sorting mechanism for extracellular matrix proteins in the TGN. This process relies on the actin cytoskeleton, the TGN-localized Ca²⁺-ATPase SPCA1, and the luminal Ca²⁺-binding protein Cab45. These findings laid the foundation for a novel sorting concept driven by the luminal milieu of the TGN. In this model, luminal scaffolding proteins act as sorting platforms, linking secreted proteins to specific lipids in the TGN membrane to form transport vesicles. Upon relocating my laboratory to Yale School of Medicine, we extended this principle to establish its role in insulin secretion, further advancing our understanding of TGN-driven sorting mechanisms.
What fascinates you most about the Golgi apparatus?
We know so much about it, yet so little. It is an incredibly complex and sophisticated organelle that, at first glance, seems like complete chaos. However, beneath the surface, it is remarkably well-organized and precisely timed, with each reaction seamlessly coordinated with the next. It’s a striking example of high order emerging from apparent chaos.
Do you have a career/research milestone you like to look back upon?
The first significant moment in my research journey came during my Ph.D. when I studied protein kinase D (PKD). I investigated how PKD is activated and accumulates in the nucleus of human gastric cancer cells upon stimulation with the gastric enzyme gastrin. During this time, I identified the signaling cascade and the molecular mechanisms governing the nuclear import and export of PKD.
I vividly remember conducting my first western blot to examine whether the export receptor binds to the kinase. That night, I couldn’t stop thinking about how exciting the experiment was. In fact, I was so thrilled that I returned to the lab at 2:00 a.m. to repeat it. That moment marked the beginning of my enduring excitement for experimental results. Early on, as a researcher, I faced the challenges of learning extensively and developing my ideas. However, this experience became the foundation of my journey toward independent thinking and becoming an independent researcher.
Who was/is your biggest supporter throughout your career?
My parents and my entire family have always been my most incredible supporters. They have consistently stood by me, encouraged me, and passionately advocated for my work. Professionally, Vivek Malhotra has been an invaluable mentor and inspiration.
What advice would you give yourself looking back, say, 20 years?
Focus on your own journey and resist the urge to compare yourself to others. Your path is unique, and success will follow if you cultivate passion and internal motivation. These qualities will stay with you and guide you through challenges. If I had allowed anxiety to consume me, I wouldn’t have made it. Fortunately, I always had a PI who believed in me, even when plagued by self-doubt. Their confidence in my potential gave me the reassurance and support I needed to persevere.
Who, what, when, where & why?
Who?
- would you like to conduct research with if you had the chance?
Tom Rapoport.
What?
- do you like to do in your free time?
Sports – running, Zumba, weightlifting. I also love opera, culture, and my friends.
When?
- do you find inspiration for your research?
I find the most inspiration for my research when writing grants. The extensive reading required sparks new ideas and thoughtful concepts. While grant writing can be tedious, it has significantly expanded my portfolio and deepened my knowledge.
Where?
- is your favorite travel destination?
California
Why?
- did you choose your specific research topic(s)?
As mentioned before, when I first met Vivek Malhotra, I was deeply impressed by his creative thinking. In general, the Golgi and membrane biology field is filled with individuals who bring incredible spirit and passion to their work.
I had to give my first significant talk at a membrane biology conference because my postdoc advisor could not attend, so I stepped in to replace him. All the big names in the field were sitting in the front row. Despite my nerves and limited experience, it went fantastically. They were incredibly supportive, recognizing that I was young and just starting. Their warmth and the way they welcomed me into the community left a lasting impression and made the experience truly rewarding.
How?
- do you deal with setbacks?
This is actually one of my strengths. While setbacks may frustrate me for a few days, I always find a renewed determination that pushes me forward. Instead of giving up, I use challenges as motivation to improve and grow stronger.
…or?
Attend a party or be the host?
Be the host.
Museum or movie theatre?
Museum.
Sneakers or dress shoes?
Sneakers.
Optimist or pessimist?
Optimist - I was a strong pessimist until I came to the USA.
Ambition or comfort?
Ambition.
See the future or change the past?
See the future.
The interview was conducted by Nicole Kilian and has been edited and condensed for clarity.
Image sources: Julia von Blume.
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