Genetics & Science
New research
New research provides a glimpse into exactly how cells in the heart start beating.
In a study conducted in zebrafish, researchers were surprised to discover that heart cells start beating all at once, and quickly become regular. Moreover, each heart cell has the ability to beat on its own, without a pacemaker, and the heartbeat can start in different places..
In the first video, heart cells are labeled with green fluorescent protein, which becomes brighter when calcium levels spike during each heartbeat. The second video shows a high-resolution look at the first beats of a developing zebrafish heart.
New research
Understanding the fundamental mechanisms underlying the heartbeat is critical for understanding what is happening in situations where the cardiac system that regulates the heartbeat doesn’t develop properly or begins to malfunction.
“The heart beats about 3 billion times in a typical human lifetime, and it must never take a break,” said co-senior author and Harvard professor Adam Cohend. “We wanted to see how this incredible machine first turns on.”.
Nonspecific immune response
The innate immune system
Is the body's first line of defense against germs entering the body. It responds in the same way to all germs and foreign substances, which is why it is sometimes referred to as the "nonspecific" immune system.
Cell division
Real microscopic footage of cell division.
Brown fat cells can use energy to produce heat, which makes them attractive tools for treating diseases like type 2 diabetes. But their potential hasn’t yet played out, in part because scientists don’t understand how brown fat develops from stem cells.
Researchers at HMS have now identified a set of cell signaling cues that lead to brown fat formation in mice (image 3) and used those signals to create human brown fat cells in a dish (images 1 and 2).
The work made use of machine-learning tools and single-cell RNA sequencing.
By offering a way to reliably produce human brown fat cells in the lab, the work could help scientists develop cell therapies for chronic diseases affecting the heart, blood vessels, and metabolism.
The findings, led by the lab of Olivier Pourquié, were published in Developmental Cell.
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3D Cell culture models
3D Cell culture models
3D Cell culture models
3D Cell culture models
Cells in the human body stick to one another and communicate through proteins on their membranes known as cell adhesion molecules, or CAMBs
The Team used HelixCAMs to create large, intricate cellular structures and influence the interactions cells adhere naturally as seen in these colorful fluorescent images.
The door opened to a better understanding of how wounds heal, how immune cells locate pathogens, and how to build living tissues for therapeutic applications.
Findings were published in the Journal Cell
The Thymus gland shows that it is the birthplace and training ground of T-cells. A new study shows how thymus cells teach the immune system how to distinguish friends from foes.
A cross-section of the spinal cord showed different types of neurons involved in touch.
A new study shows that tumor cells with particular mutations in a gene called isocitrate dehydrogenase (IDH) release metabolite (D-2HG) that weakens nearby immune cells (CD8 + T cells) rendering them less capable of killing cancer cells.
Invasive melanoma cells (red) are surrounded by two types of immune cells: myeloid cells (green) and T cells ( blue). In this case, the immune cells are unable to infiltrate the tumor and kill the cancer cells.
Multiplexed RNA imaging of part of the human brain was used to produce this image, which shows RNA molecules (various colors) expressed from 4,000 different genes in individual cells.
The Zhuang lab at HMS develops novel imaging methods, molecular probes, and image analysis algorithms, and uses these tools to study a variety of biological problems. The research that produced this image involved the development of high-resolution, spatially resolved single-cell imaging methods that can be used to study how the spatial and molecular architecture of the mammalian brain alters during evolution and in diseases.
Photo: Rongxin Fang, postdoctoral fellow
Researchers use the fruit fly larval brain, shown here, to study glioma, a type of brain tumor. The different types of brain cells shown include glial cells (blue), which support, nourish, and protect neurons, glial nuclei (red), and neuropils (green), which are dense networks of fine glial processes and neuronal processes (axons and dendrites).
Neurofibromatosis type 1 is a genetic disease characterized by tumors of the nervous system. Assistant Professor James Walker’s lab has developed fruit fly models of the disorder and uses them to improve our understanding of the mechanism that drives neurofibromatosis type 1, with the goal of identifying potential therapeutic targets.
Photo: Torrey Mandigo, postdoctoral fellow
Understanding how the blood-brain barrier — the vital layer of protective cells around the brain and spinal cord — works to allow in or keep out certain substances has critical implications for everything from disease progression to drug delivery. Now, a discovery has brought scientists one step closer to figuring it out.
Working in zebrafish and mice, researchers discovered that a signal originating from a gene (spock1) in neurons is essential for the proper formation of the blood-brain barrier during embryonic development and helps ensure that the barrier remains intact throughout adulthood.
In the first image, researchers injected fluorescent dye (blue) into the circulatory system of a zebrafish with a spock1 mutation. The dye leaked out of blood vessels (pink) in the forebrain and midbrain (left), but stayed relatively confined within the hindbrain (right), revealing a blood-brain barrier that was permeable in some areas but not others.
In the second image, a time-lapse shows a tracer (yellow) accumulating in the brain of a zebrafish with a spock1 mutation over the course of an hour. The tracer is moving out of blood vessels, whose blood-brain barrier was made permeable by the mutation, into the surrounding brain.
If replicated in further animal testing and eventually in humans, the findings could help scientists control the blood-brain barrier — important for delivering drugs into the central nervous system or countering damage from neurodegenerative disease.
Images: Natasha O’Brown
This photo was captured using ultrahigh-resolution diffusion magnetic resonance imaging. It shows previously invisible u-shaped connections of the superficial white matter of the human brain. The colors indicate the overall 3D orientation of fibers in the brain and their estimated white matter connections.
Lauren Jean O’Donnell’s lab at HMS is working to create the first atlas of the human brain’s superficial white matter. Located between the deep white matter and the cortex, the superficial white matter plays an important role in neurodevelopment and aging and has been implicated in a large number of diseases, yet is vastly underrepresented in current descriptions of the human brain connectome.
The creation of comprehensive, anatomically curated maps of the superficial white matter would allow it to be studied in health and disease.
Photo: Fan Zhang, former HMS instructor in radiology, Brigham and Women’s Hospital
A new tool, called Orion, combines structural details with molecular information about tumors to create a new image of a tumor sample. Pathologists can use the integrated image to delve deeper into the details of a tumor, with the ultimate goal of improving cancer diagnosis and treatment.
With Orion, pathologists can identify an area of interest on a tumor sample based on molecular details from immunofluorescence imaging, and overlay structural information using a “lens” of histology staining (circle). In this case, the histology lens hovers over the border where normal cells (left) transition into colorectal tumor cells (right). Immunofluorescence imaging identifies specific types of immune markers present (various colors), while histology staining shows how immune cells (purple) are clustered around glands in the intestine (white ovals inside circle).
Image: Santagata and Sorger labs
This image of the vasculature in the developing cochlea was created by Katelyn Comeau in the Lab of Lisa Goodrich at Harvard Medical School. It was selected as a winner of the Harvard Brain Institute’s 2022 Beauty of the Brain image contest.
It shows the apex of the snail-shaped cochlea, our hearing organ, with a dense plexus of vasculature, shown in green. The hair cells, which detect sound, are shown in magenta and are innervated by the primary auditory neurons, whose cell bodies and axons are also in magenta.
This image shows a cross-section of the mouse nasal epithelium. Olfactory sensory neurons (yellow) detect volatile odorants and relay this information via their axons (magenta) directly into the brain, where they coalesce into structures known as glomeruli in the olfactory bulb, on top. Nuclei are stained with DAPI (cyan).
Created by David Brann in the Lab of Bob Datta at Harvard Medical School, this image was selected as a winner of the Harvard Brain Science Institute’s 2022 Beauty of the Brain image contest.
Although the human body is externally symmetric across the left-right axis, there are remarkable left-right asymmetries in the shape, size, and positioning of many internal organs, including the heart, lungs, liver, stomach, and brain. These asymmetries can range from benign to serious, causing a range of conditions that affect multiple organs.
Developmental biologists have long been fascinated by how this asymmetry arises in the first place.
Now, scientists have identified a key player in the mechanism that shapes left-to-right organ placement in the body. The work shows that cilia—tiny whip-like projections on the surface of cells—act as sensors for the forces that shape organ placement.
The findings advance understanding of the fundamental cellular processes that govern the development of the human body and may lead to the development of novel diagnostics of to treat disorders associated with defects in left-right asymmetry.
Mitosis stages
The five phases of mitosis and cell division tightly coordinate the movements of hundreds of proteins.
The process by which a cell replicates its chromosomes and then segregates them, producing two identical nuclei in preparation for cell division.
Fertilization and Implantation
Sperm fuse with egg occurs in this portion of the tube. The fertilized egg then begins a rapid descent to the uterus. The stages of fertilization can be divided into four processes: 1) sperm preparation, 2) sperm-egg recognition and binding, 3) sperm-egg fusion, and 4) fusion of sperm and egg pronuclei and activation of the zygote.
The Potential of Zygote
From one diploid cell to new organism.
Scientist: Dr. Alireza Kamali Dehkordi
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