Exploring the 2024 Hooke Medal winner's groundbreaking research on how cells create diversity through unequal division
In the microscopic universe within our bodies, a profound and elegant process repeats itself countless times each day, shaping our development and sustaining our health. This process is asymmetric cell division—a remarkable biological event where one mother cell divides to produce two daughter cells with different identities and destinies. It is the cellular equivalent of a single parent giving birth to twins who grow up to pursue completely different careers. For his groundbreaking work in unraveling the mysteries of this fundamental biological phenomenon, Dr. Emmanuel Derivery, a Group Leader at the MRC Laboratory of Molecular Biology (LMB), was awarded the prestigious 2024 Hooke Medal by the British Society for Cell Biology 1 .
Awarded to Dr. Emmanuel Derivery for outstanding contributions to cell biology, particularly in understanding asymmetric cell division.
Intersection of biology, chemistry, and physics to understand how cells distribute components unequally during division.
At first glance, cell division might appear to be a simple matter of duplication and splitting. However, asymmetric cell division represents a far more sophisticated and carefully orchestrated process. In this biological ballet, a mother cell distributes its cellular contents unequally between two daughter cells, allowing them to adopt different functions and fates 1 .
Crucial for maintaining stem cell pools while producing specialized cells
Transforms a single fertilized egg into complex tissues and organs
Errors can lead to cancer and neurodegenerative diseases
Dr. Derivery's research focuses on how cell fate determinants—key protein molecules that dictate a cell's future—are segregated asymmetrically during division 1 .
One of the most significant challenges in studying asymmetric cell division in mammals has been the complexity of the process and the difficulty in controlling it experimentally. Traditional approaches involved observing what happens when specific genes are disrupted, but this often provided limited insight into the precise mechanics of how asymmetry is established and maintained.
Engineer cellular asymmetry on demand
Create endocytosis-resistant clusters
Spontaneous coalescence during division
Dr. Derivery's team pioneered an innovative solution to this problem: rather than just observing nature, they developed a method to engineer cellular asymmetry on demand. As detailed in a key protocol published by Springer, they created a synthetic biology approach that allows them to induce cortical polarity of virtually any protein of interest in otherwise unpolarized cultured mammalian cells 2 .
The approach uses a de novo-designed 2D protein polymer to cluster a stably expressed transmembrane segment from outside the cell 2 . These clusters, uniformly spread during most of the cell's life, spontaneously coalesce into an asymmetric cortical cap when the cell rounds up for division.
To truly appreciate the significance of Dr. Derivery's work, it is valuable to understand one of his key experiments in detail. This experiment demonstrates how his team successfully engineered asymmetry in mammalian cells and observed the resulting effects on cell division.
Mouse fibroblasts (3T3 FlpIn cells) were engineered to stably co-express several components including a transmembrane construct and fluorescent markers 2 .
Imaging dishes were coated with fibronectin to promote cell adhesion.
Cells were incubated with protein components to form stable clusters on the cell surface 2 .
In mitotic cells, clusters spontaneously coalesced into a single, asymmetric cap.
Effects were analyzed using spinning disk confocal microscopy.
| Component Name | Molecular Weight | Function in Experiment |
|---|---|---|
| A(d) | 30 kDa | First polymer component; forms structural framework for clusters |
| B(c)-GFP | 70 kDa | Second polymer component fused to GFP; allows visualization of clusters |
| GBP-TM-GBP | N/A | Transmembrane anchor that connects extracellular clusters to intracellular space |
The results of this elegant experiment were striking. In interphase cells, the engineered clusters remained uniformly distributed. However, as cells entered mitosis, these clusters spontaneously migrated and coalesced to form a single, bright asymmetric cap at one pole of the cell 2 .
The mitotic spindle rotated to align along the engineered polarity axis, mimicking natural asymmetric divisions.
Formation of asymmetric central spindle with different microtubule density on each side.
| Cellular Process | Observation in Engineered Cells | Biological Significance |
|---|---|---|
| Cortical Cap Formation | Clusters coalesced into asymmetric caps in mitotic cells | Reproduced the polarized cortex of naturally asymmetric cells |
| Spindle Alignment | Mitotic spindle rotated to align with engineered polarity axis | Ensures proper orientation for asymmetric division |
| Central Spindle Morphology | Formation of asymmetric central spindle with different microtubule density | May influence differential inheritance of cellular components |
| Cell Fate Determination | Differential distribution of proteins to daughter cells | Creates daughter cells with different molecular identities |
Dr. Derivery's research relies on a sophisticated array of biological tools and reagents that enable the precision engineering of cellular processes. These resources represent the cutting edge of modern cell biology technology.
| Reagent/Resource | Function and Application |
|---|---|
| De Novo Designed 2D Protein Polymers | Artificial proteins designed to form stable clusters on cell surfaces |
| BL21 E. coli Bacteria | Used to produce the designed protein components in large quantities |
| 3T3 FlpIn Mouse Fibroblasts | Mammalian cell line engineered for consistent gene expression |
| GFP and iRFP670 Fluorescent Markers | Protein tags that allow visualization of cellular components |
| Spinning Disk Confocal Microscope | Advanced imaging for real-time observation of living cells |
| NiNTA Purification Columns | Used to isolate and purify his-tagged protein components |
| Superdex 200 Gel Filtration Column | Separates proteins by size for quality control |
The recognition of Dr. Derivery with the 2024 Hooke Medal acknowledges not only his specific contributions to understanding asymmetric cell division but also the broader potential of his innovative approaches to advance cell biology as a discipline. His work demonstrates the power of combining quantitative imaging, in vitro reconstruction, and de novo protein design to tackle previously intractable biological questions 1 .
Controlling asymmetric division could lead to improved methods for growing replacement tissues and organs.
Understanding defects in asymmetric division could reveal new therapeutic targets for cancer treatment.
Conditions from embryonic development errors might be better understood through this research.
The integration of de novo protein design—creating molecular machines from scratch—with classical biological approaches promises to unlock even deeper mysteries of cellular organization and function. Dr. Derivery's work exemplifies how technological innovation drives biological discovery, providing new tools to answer old questions while revealing new ones we have only begun to imagine.