The Illuminators: Scope for Change 2021

This image shows the microstructure of beef mince tissue, where proteins are red and lipids are white.

This image shows a unique population of connective tissue cells within the aortic valve of a mouse’s heart.

These cells express both our red and green proteins of interest, but the image has been artistically shifted to the right such that the two colours no longer overlap. The DNA containing nucleus in each cell is shown in blue.

We believe this red/green population may be involved in the repair and regeneration of the heart.

Macrophages - "Big Eaters" in Greek - are cells of the immune system that eat harmful bugs and debris within our body to keep us healthy.

This macrophage (blue) is eating beads (yellow) that have been coated with parts of fungi. Coincidentally, the macrophage is also preparing to undergo cell division as the nucleus (pink), which contains the cell’s DNA, is beginning to split into two.

This video captures ‘cell drinking’, wherein breast cancer cells (blue) are engulfing fluorescently labelled sugars (yellow/pink) in the nutrient media.

Some cancer cells can indiscriminately gather nutrients from the media or cannibalize each other in order to sustain themselves. By understanding the mechanism that controls ‘cell drinking’ in cancer cells we can target them and thereby stop their growth.

This image shows that when human cancer cells are placed on a chicken embryo blood vessel network, they can form a tumour (top) that is fed nutrients from the embryo’s blood vessels (bottom, white).

This sample has also been treated with nanoparticles (green) that can penetrate the solid tumour. In future, these tumour-infiltrating particles could contain new cancer-killing drugs.

This image was taken in collaboration with Florence Tomasetig at the KGLMF.

This image shows a single neuron derived from the brain of a monkey. You can clearly see the different structures of the cell, from the round cell body in the centre to the long axon and spiny dendrites spreading out. This work will give us more clues as to how the brain receives and processes visual information relayed from our eyes.

CATFISH fluorescent technique has been used to reveal the skeletal network (green) supporting the DNA-containing nucleus (blue) in neurons from a rat brain. The red proteins move outside of the nucleus when the neurons are treated with methamphetamine. This work will help us determine how drugs like methamphetamine effect brain function and lead to addiction.

These images demonstrate how the architecture of the mammary gland (breast) dramatically changes over the course of pregnancy and pup-bearing in a mouse. During pregnancy (left panel), the gland begins to develop bulbous structures that grow bigger and stretch over time as they start filling with the milk that will feed the young after birth (middle panel). Once the pups are old enough and no longer need their mother’s milk to survive, these structures will stop producing milk and deflate (right panel), ultimately destroying themselves to return the gland to a pre-pregnant state – ready for the next round of pregnancy.

Oxytocin is known as the ‘love’ hormone and is released into the mother’s system during breast-feeding. This video shows living, milk-producing structures (purple) in the mammary gland (breast) of mice that are in the late stages of pregnancy. When we add oxytocin to the gland, the amount of calcium within the cells increases (yellow). This causes the cells to contract, squeezing out the milk that would then (naturally) make its way into the feeding pup’s mouth. If we can learn more about calcium in these processes, we’ll be able to help mother’s experiencing difficulty breast-feeding.

As a researcher of psychology and ageing who returned to studies as a mature student in her thirties while raising children as a single parent, continuing on with post-graduate research, I would like to communicate through as many diverse avenues as possible the importance of women being able to see a future in research beyond their 'child-rearing' years.

My work is in psychology and behaviour, and is in creating age-friendly spaces. The photos presented here are microscopic images of my changing hair colour, metaphorically demonstrating that we are slowly moving out of the ‘dark age’ and into the light when it comes to supporting women of any age in STEMM. Paradoxically, we are asking to hold the space for these visible life changes of dark to light shades of silver and grey hair and recognise that women over forty and fifty are also competent contributors to STEMM fields.

Bringing the intersectionality of women and ageing into the STEMM space, is equally important for younger women who will see that they can not only change careers, but also continue on after they have had children too.

I am studying a type of bacteria – called Streptomyces – in Antarctic soil to understand the environmental impact of their activity there. A major focus of my work is on a new form of growth associated with the way they slide around.

This image shows a colony of Streptomyces, where the live bacterial cells within the colony fluoresce green.

I think this colony looks like the shape of Australia, and reminds me of the initiative and strong commitment of this country to understand the role of bacteria in the Antarctic ecosystem.

This image shows the accumulation of specific immune cells (green) within the connective tissue (blue) and other components (red) of ear skin from mice. With this mouse model, we can study how immune cells move to sites of tissue damage in real time. We can then use this information to identify important elements in the wound healing response and ultimately exploit these elements to improve healing in scarred tissue and non-healing wounds (tumours).

Each photo in this gallery shows a single, living cell. In the top row, the cells are grown on a flat surface and can more easily spread their little arms out, sensing the environment completely. Can you spot one that looks like a fish?

In the bottom three rows, the cells are grown on a bed of soft, plastic pillar structures that poke into the cell (white circles, sometimes with a dark ring, representing the accumulation of cellular components). Because it's harder for these cells to spread out, they tend to keep their arms to themselves and therefore adopt a more rounded shape.

I think this makes them look like emojis – how many faces can you see?

(Thank you to Jess Richardson for the gallery inspiration!)

Protein nanowires – more than 2000 times thinner than a strand of human hair – allow electrons to hop from one end to the other of protein filaments. Our experiments revealed that a single protein nanowire was capable of conducting electricity. This means that we can use these nanowires to build miniature bioelectrical devices.

Yes, they can – and what’s more, it’s this sense of smell that helps the sperm reach the egg and makes fertilisation possible.Sperm contain olfactory molecules that interact with chemical odours generated by eggs in the female reproductive system.

This image shows two such olfactory molecules (red and green) in an activated and fertile human sperm cell. This image has been adapted from Makeyeva, Y et al., Immunocytochemical localisation of olfactory-signaling molecules in human and rat spermatozoa, Journal of Histochemistry and Cytochemistry (Volume 68, Issue 7) pp. 491-513. Copyright 2020 (SAGE Publishing). DOI: 10.1369/0022155420939833.

Microscopy has evolved to enable us to visually observe how new therapeutic drugs affect tumours in living mice, in real time. We can then use this information to improve our understanding of how, when and where the drugs work, and which ones are better candidates for clinical trials.

This image shows pancreatic cancer cells (blue) surrounded by connective tissue (magenta) in the tumour of a live mouse.

This video showcases the hind limb of a special strain of guinea pig that spontaneously develops osteoarthritis with age, just like us!

The femur is at the top and the proximal tibia is on the right. These bones are surrounded by muscle (green) and blood vessels. A glowing red tracer can be found in both the blood vessels and bone marrow; we use this tracer to investigate how osteoarthritis affects the travel of molecules from (and between) the blood and bone, as well as the entire joint. Through our work, we’ll be able to develop new treatments for osteoarthritis.

This video moves through 3192 individual images that have been stitched together and represents 43+ hours of continuous imaging on a microscope.

This is the spiral structure of the mouse cochlea, showing neurons (green) and a special population of cells that express our gene of interest (red). These special cells are usually found at the very bottom of the spiral, which is an understudied region. We’re currently deciphering how this unique population contributes to hearing in mice.

The importance of the 3D structure of the cochlea lends itself exquisitely to the power of 3D imaging systems.

Each feature in this atomic force microscopy image is an individual protein that can form a pore on the surface of bacteria known as Deinococcus radiodurans. These proteins naturally form sheets of hexagonally packed features. If you look closely you can see that the pore in the centre of some individual proteins is in the open state. Each individual protein is approximately 4 nm wide (or 1/250000 mm).

Here a neuronal cell has been labelled with a green marker and grown on a flexible bed of cylinders coated with a connective tissue protein, labelled here in magenta. Extensions called neurites grow out from the cell over the tops of these flexible cylinders. We use this setup to study how the neurons react to "touch" by gently moving an individual cylinder under the neurite and measuring the cell response.

This work is under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License and has been adapted from Poole, K et al. (2014), Nature Communications, DOI: 10.1038/ncomms4520.

Birds are capable of "mechanical synthesis" - even with a small brain, they can arrange sticks and twigs systematically to build a nest with the desired mechanical properties. Cells, although brainless, are too capable of arranging their skeletal filaments in such a way, adapting to their local mechanical environment.

Nature is indeed smarter than we think.

Specialised cancer cells drive the spread of cancer around the body and the development of treatment-resistant disease. These aggressive cells, termed cancer stem cells, form three-dimensional spheroid structures (pictured). Spheroids are a useful tool to study the mechanisms that enable cancer stem cells to grow. We hope that these studies will uncover new therapeutic strategies to create improved therapies for patients.

This cell has been cultured on an array of microscale elastic cylinders that can be gently poked to apply tiny mechanical forces to the cell (as in the cartoon above). These forces result in the opening of channels on the cell’s surface, which sense and then convert these forces into a signal that the cell can understand – in this case, in the form of calcium entry into the cell. Calcium influx is visualised as the white wave moving across the cell.

The video was made by combining still images one after another, some of which appear in a published paper. Reprinted with permission from Bavi, N et al. (2019), American Chemical Society, DOI: 10.1021/acsnano.9b07499. Copyright 2019 American Chemical Society.

All living cells, starting from bacteria to humans, have biological energy generators that convert energy from the food we eat into the energy currency that the body can utilise. We used cryo-Electron Microscopy to study the detailed structure of this protein complex from bacteria which in turn enabled us to understand how this generator flexes and moves, providing a detailed molecular understanding of the functioning of the complex. Once we understand their fundamental biology, we can start thinking about what happens to the machine when things go wrong; for example, during a disease. The image is cryo-Electron micrograph and 2D classification of a part of the energy generator. The movie shows how we interpret the structural data obtained from the microscope to understand the steps and detailed working of the motor.

This video is under the Creative Commons Attribution 4.0 International License (Creative Commons — Attribution 4.0 International — CC BY 4.0) and has been adapted from Sobti, M et al. (2021), Nature Communications, DOI: 10.1038/s41467-021-25029-0 (figure labels removed).

SARS-CoV2 virus uses the spike protein located on its surface to enter human cells; therefore, it is an ideal target for vaccines and antiviral treatment. Antibodies are molecules produced by our immune system to fight any kind of infection. We use cryo-Electron Microscopy to study lab-modified variants of human antibodies produced against the SARS-CoV2 spike protein, to choose the best molecules capable of neutralising COVID-19 virus and hence be used for treating COVID-19 positive patients. The image is a cryo-Electron micrograph and 2D classification of the SARS-CoV2 spike protein in association with antibodies. The movie shows purified SARS-CoV2 spike protein bound to two such antibodies.

A super thin section of soft coral has been dyed to show the cells (red) and connective tissue (blue). These slices can help us identify predation, diseases, and other health conditions in corals.

This animation was created from tens of thousands of 2D images stitched and stacked together to reconstruct the 3D architecture of a tumour. To capture the images the tumour was made transparent to allow light to penetrate through it. The blood vessels (red) and type of immune cell (green) were modified to express a protein that emits light when excited by a laser. The immune cells seem to be floating inside the tumour but they are actually squished between the transparent tumour cells.

Reprinted from Journal of Investigative Dermatology, Vol 141, Tikoo S et al., Amelanotic B16-F10 Melanoma Compatible with Advanced Three-Dimensional Imaging Modalities, P2090-2094, Copyright (2021), with permission from Elsevier. Home Page: Journal of Investigative Dermatology (jidonline.org)

This image represents the arteriole blood vessel network (red) of a rat spinal cord and some of the most external layers of the astrocytes composing it (green). The spinal cord was chemically treated to become transparent prior to imaging. The images are snapshots of the 3D rendered data set acquired at different angles.

This work is done in collaboration with Professor Lynne Bilston from NeuRA institute.

Imagine looking down a microscope to see another world, with an unexpectedly bright sky scattered with little dark stars across the field.

Each of these star-like structures are actually groups of six tiny proteins that are bound together to make this shape. The proteins come from HIV and play a critical role in HIV's ability to infect people.

Here, these proteins have been separated from the virus and frozen in a very thin layer of ice. They are then photographed using an electron microscope, which can focus on objects that are only nanometres wide. Due to the freezing aspect, this technique is called cryogenic electron microscopy.

Pancreatic tumours are known for stimulating connective tissue scarring (green). This response not only makes the tumours more aggressive, but also renders tumours largely inaccessible by cancer-killing drugs. We are looking for new ways to stop both the cancer cells (red) and the scarred tissue (green), and as our protein-of-interest marks both populations (yellow) it could be a great target. As such, our work provides us with a strategic insight for the development of new, tumour-penetrating drugs.

Reprinted from Cancer Research, 2021, 81(13), 3461-3479, Sharbeen G et al., Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition, with permission from AACR.