SEEING WHAT CANNOT BE SEEN

Electron microscopy images captured by Carnegie Embryology's Mike Sepanski

Microvilli like fingers, DNA like tangled ropes, lipid droplets like oil in water: Mike Sepanski’s work exists at the intersection of art and science, revealing familiar forms in an unfamiliar world.


Sepanski captured the following images using transmission electron microscopy (TEM) at the Carnegie Institution for Science, Department of Embryology. TEM uses electrons, rather than light, to visualize details 100 times smaller than can be seen with light microscopes—features as small as individual molecules. This process requires great skill and is enormously useful to scientists who study life at the subcellular level. It also requires an artistic eye capable of picking meaningful compositions from images of life on a scale impossible to experience directly.


In January 2021, Mike Sepanski retired from Carnegie after a 37-year career. To celebrate his tremendous contributions to science at the Department of Embryology and beyond, we have put together this gallery of his otherworldly images.


The following samples were prepared by the scientist cited in bold and imaged by Mike Sepanski.

SYMBIOSIS

Many corals rely upon photosynthetic algae that live inside individual coral cells, sharing nutrients in a relationship called endosymbiosis.

Corals are tiny animals that build elaborate skeletons which accumulate to form reefs. Environmental stressors can disrupt the symbiotic algae, leading to coral death and bleaching. In these images of a Xenia coral, Sepanski captures the symbiotic coral cell that houses the algae, revealing its intricate structures that are lost during bleaching. // Minjie Hu / 2019
Corals are tiny animals that build elaborate skeletons that accumulate to form reefs. Environmental stressors can disrupt the symbiotic algae, leading to coral death and bleaching. In these images of a Xenia coral, Sepanski captures the symbiotic coral cell that houses the algae, revealing its intricate structures that are lost during bleaching. // Minjie Hu / 2019
Imaging both the coral and the algae together presented a technical challenge because the coral cells are soft, whereas the algae are encased in a thick, hard cell wall, which is difficult to cut without damaging the coral. Sepanski had to embed the animal tissue in a hard plastic that matched the hardness of the algae. // Minjie Hu / 2019
Imaging both the coral and the algae together presented a technical challenge because the coral cells are soft, whereas the algae are encased in a thick, hard cell wall, which is difficult to cut without damaging the coral. Sepanski had to embed the animal tissue in a hard plastic that matched the hardness of the algae. // Minjie Hu / 2019

REPRODUCTION

Carnegie scientists study the genes that control reproduction in all animals by using the fruit fly, Drosophila melanogaster, as a model. Model organisms aid researchers by speeding up the time and reducing the cost of experiments, making science more efficient.

Sperm cells are stored in the female fruit fly after mating. Nutrients are secreted into a duct that crosses the cuticle to reach the sperm, seen as pinwheel shapes below the cuticle. // Allan Spradling / 2008
Sperm cells are stored in the female fruit fly after mating. Nutrients are secreted into a duct that crosses the cuticle to reach the sperm, seen as pinwheel shapes below the cuticle. // Allan Spradling / 2008
The ring canal, which carries materials from a nurse cell to the oocyte is shown here in cross-section. Electron microscopy images of cells often look grainy due to the staining of individual molecules. The dark grains in this image are called ribosomes, which are large molecules of RNA that translate the instructions contained in genes into the proteins that make cells work. // Allan Spradling / 2001
The ring canal, shown here in cross-section, carries materials from a nurse cell to the oocyte. Electron microscopy images of cells often look grainy due to the staining of individual molecules. The dark grains in this image are called ribosomes, which are large RNA molecules that translate the instructions contained in genes into the proteins that make cells work. // Allan Spradling / 2001
Unique model organisms allow for specialized study of certain reproductive processes. The fungus gnat has one giant nurse cell that has many extra chromosomes and is attached to one oocyte. // John Urban / 2020
Each model organism has certain traits that make it ideal for investigating specific biological processes. The fungus gnat has one giant nurse cell that has many extra chromosomes and is attached to one oocyte. // John Urban / 2020
The mouse is an essential model organism because it allows the study of mammalian processes. The synaptonemal complex, seen as a tangled cluster is the structure essential for recombination in meiotic germ cells and ensures that each sperm or egg cell carries a unique set of genes. // Alex Bortvin / 2020
The mouse is an essential model because it allows the study of mammalian processes. The synaptonemal complex, seen as a tangled cluster, is critical for recombination in meiotic germ cells and ensures that each sperm or egg cell carries a unique set of genes. // Alex Bortvin / 2020

BOUNDARY LAYERS

Organs are largely defined by the membranes that divide them into discreet compartments. Boundary layers are defined where a fluid comes in contact with a surface. Signals and nutrients selectively cross these boundaries, a source of organization crucial for the function of organisms.

An organism's intestine is specialized for the absorption of nutrients from its diet. When a Zebrafish consumes a high-fat meal, the intestinal epithelial cells absorb and temporarily store some of these lipid molecules in lipid droplets which appear as small light-colored circles. // Meredith Wilson / 2015
An organism's intestine is specialized for the absorption of nutrients from its diet. When a Zebrafish consumes a high-fat meal, the intestinal epithelial cells absorb and temporarily store some of these lipid molecules in lipid droplets which appear as small light-colored circles. // Meredith Wilson / 2015
The peritrophic membrane is a selective barrier that lines the Drosophila gut. It begins as a compact roll, before unfurling into a larger tube that lines the rest of the gut. // Ren Dodge / 2020
The peritrophic membrane is a selective barrier that lines the Drosophila (fruit fly) gut. It begins as a compact roll before unfurling into a larger tube that mediates the exchange between the food and microbes inside with the fly's intestine. // Ren Dodge / 2020
A giant nurse cell and adjacent follicle cells. // John Urban / 2020
A giant nurse cell and adjacent follicle cells. // John Urban / 2020

JUMPING GENES

Alterations to the structure or sequence of DNA can cause mutations, leading to disease or the evolution of a species. Transposons, or "jumping genes," are sections of DNA that move from one location on the genome to another, altering the sequence unpredictably. Transposons were discovered at the Carnegie Institution for Science by Barbara McClintock, earning her a Nobel Prize in 1983.

Here, Sepanski captures the transposon in the act of forming an aggregate of virus-like particles surrounding a membrane (black lines) in a mouse male germ cell. // Alex Bortvin / 2020
Here, Sepanski captures the transposon in the act of forming an aggregate of virus-like particles surrounding a membrane (black lines) in a mouse male germ cell. // Alex Bortvin / 2020
Specially designed antibodies (black dots) identify the location of a transposon-hunting protein, Maelstrom, in the chromatoid body of a mouse male germ cell. // Alex Bortvin / 2020
Specially designed antibodies (black dots) identify the location of a transposon-hunting protein, Maelstrom, in the chromatoid body of a mouse male germ cell. // Alex Bortvin / 2020

OIL IN WATER

The tendency of fatty acids and similar molecules to form droplets in water has profound implications for life. Lipids, present as subcellular droplets, can store energy, act as chemical messengers, or deliver essential nutrients - these fatty bubbles have even proven to be the best delivery vehicle for the mRNA Covid-19 vaccine.

Zebrafish embryos develop outside of the mother's body and rely on maternally-deposited yolk stores to provide the energy and building blocks needed for development. When the transfer of yolk lipid to the body is blocked, the lipid accumulates abnormally in cytoplasmic lipid droplets. // Meredith Wilson / 2018
Zebrafish embryos develop outside of their mother's body and rely on maternally-deposited yolk stores to provide the energy and building blocks they need to develop. When the transfer of yolk lipid to the body is blocked, the lipid accumulates abnormally in cytoplasmic lipid droplets. // Meredith Wilson / 2018
Loss of the tm6sf2 gene produces lipid droplets in unfed intestinal enterocytes // Steve Farber / 2015
Loss of the tm6sf2 gene produces lipid droplets in unfed intestinal enterocytes. // Steve Farber / 2015

IMMORTAL CELLS

Immortalized cells derived from cancer patients are often used in biological research because they can multiply indefinitely. The K562 human lymphoma cell line (seen below) is used to study the degradation of ribosomes.

The nucleus, which takes up most of this cell, is bounded by the nuclear membrane seen as a thick, dark line. Sepanski must balance capturing pertinent molecular details with the impressions that the images give to viewers. // Kamena Kostova / 2020
The nucleus, which takes up most of this cell, is bounded by the nuclear membrane (seen as a thick, dark line). Sepanski must balance capturing pertinent molecular details with the impressions that the images give to viewers. // Kamena Kostova / 2020

STRUCTURES

The structures formed at a microscopic level are striking in their complexity. The mechanics of these forms have a significant impact on the function of tissues. Tubes, furrows, and fibrils transmit the biology of the microscopic to the anatomy of the macroscopic.

A long, tubelike structure, the malpighian tubules of the fruit fly are analogous in function to the human kidney. // Chenhui Wang / 2020
A long, tubelike structure, the malpighian tubules of the fruit fly are analogous in function to the human kidney. // Chenhui Wang / 2020
Kidney stones form in the malpighian tubule of an ry506 mutant fly. // Chenhui Wang / 2020
Kidney stones form in the malpighian tubule of a ry506 mutant fly. // Chenhui Wang / 2020
This section of a fruit fly's esophagus reveals a network of crypts housing symbiotic bacteria. Sepanski took special care to preserve the fluid contents of the esophagus, which could shift or become distorted during the preparation for imaging. // Ren Dodge / 2020
This section of a fruit fly's esophagus reveals a network of crypts housing symbiotic bacteria. Sepanski took special care to preserve the fluid contents of the esophagus, which could shift or become distorted during the preparation for imaging. // Ren Dodge / 2020
A tendon in cross section. The dark cell with extensive endoplasmic reticulum network is a tenocyte, which is surrounded by collagen fibrils that it secretes. Here, Sepanski balances contrast between the dark-staining endoplasmic reticulum and the light-staining collagen to produce a dramatic effect. // Chen-Ming Fan / 2019
A tendon in cross-section. The dark cell with an extensive endoplasmic reticulum network is a tenocyte, surrounded by the collagen fibrils that it secretes. Here, Sepanski balances contrast between the dark-staining endoplasmic reticulum and the light-staining collagen to produce a dramatic effect. // Chen-Ming Fan / 2019

MITOCHONDRIA

Mitochondria are organelles present in all plants and animals that convert energy from food into a form the cells can use. Like symbiotic organisms, these organelles possess their own genome and gene expression machinery. Disruption to mitochondrial genes can cause diseases such as Leigh Syndrome, a degenerative and often lethal condition.

Mitochondria in Zebrafish are seen as smooth ovals, defined by the outer membrane. The squiggly lines inside the oval are the inner membrane. The extensive membranes facilitate the production of energy for the cell. // Jen Anderson / 2020

Mitochondria in Zebrafish are seen as smooth ovals, defined by the outer membrane. The squiggly lines inside the oval are the inner membrane. The extensive membranes facilitate the production of energy for the cell. // Jen Anderson / 2020


Altered mitochondrial morphology in zebrafish with a mutation of the lrrprc gene recapitulates Leigh Syndrome // Jen Anderson / 2020
Altered mitochondrial morphology in zebrafish with a mutant lrrprc gene recapitulates Leigh Syndrome // Jen Anderson / 2020

The images in this gallery represent only a fraction of the Department of Embryology’s groundbreaking scientific research. To learn more about what we do, visit emb.carnegiescience.edu


The Carnegie Institution for Science, Department of Embryology has become recognized worldwide as one of the premier research centers in cellular, developmental, and genetic biology. The department has a unique atmosphere and research style that have allowed a small enterprise to have a disproportionately large impact on science. We revere this atmosphere as the source of our inspiration and strive to further improve it as the department evolves within the current milieu of intensive activity, investment, and opportunity in the biological sciences.