THE HUMAN PROTEIN ATLAS BLOG
Previously we have highlighted proteins expressed in the human neural retina. Today, we will focus on the lens and shed light on its structure and function, and hopefully spark an interest in you for the proteins of the lens.
The main function of the lens is to focus light on the retina. The passage of light through the cornea, lens and vitreous all the way to the retinal layer of the eye is only possible due to transparency of the tissue. Although the lens is very protein-rich, light absorption and light scattering in the lens is minimal.
The lens comprise of non-diving lens cells which are mainly composed of ordered proteins called crystallins...Read more
Mathias Uhlen from the Human Protein Atlas will on July the 27 present a keynote lecture on the Europe-Korea Conference on Science and Technology (EKC2017) entitled "The Human Protein Atlas - implications for human biology, drug development and precision medicine"...Read more
Let‘s have a look at the protein TPX2, a microtubule nucleation factor that translocates from the nucleus - where it resides during interphase - to the mitotic spindle during mitosis.
The mitotic spindle forms when chromosomes are ready to segregate during cell division and not surprisingly this protein is also found in this specific compartment of the cell! TPX2 is required for the correct formation of the kinetochores that is crucial for the attachment of microtubules, enabling the sister chromatids to be pulled apart...Read more
This week, Scientific American announced ten emerging technologies with innovations that are on the verge of changing society. One of the technologies selected was the Human Cell Atlas, which aims to integrate research exploring the building-blocks of human cells using new emerging technologies. The list of ten emerging technologies was compiled in a collaboration between Scientific American and the World Economic Forum's Expert Network with suggestions from members of the Expert Network, the forum's Global Future Councils and Scientific American's board of advisers...Read more
In this week's image of the week we look at G protein-coupled receptor 17 (GPR17), a member of the G protein-coupled receptor (GPCR) family, whose members serve as important regulators of oligodendrocyte development.
Oligodendrocytes are the cells that mainly provide support and electrically insulate axons in the brain by forming the myelin sheath. During development, these cells progress from oligodendrocyte precursor cells to myelinating mature oligodendrocytes. GPR17, in particular is an oligodendroglial maturation inhibitor since its stimulation arrests mouse oligodendrocytes at a less differentiated stage...Read more
We would like to thank all participants of the CYTO2017 Image analysis challenge co-organized by the Cell Atlas team. And congratulate the winner, Dr. Peng Qiu from Georgia Tech, who at the time of the challenge closing had the top solution for both Challenge 2 and Challenge 3.
Though submissions this year were high-quality, and showcased the multitude of approaches to such a challenge, there is still large room for improvements in the results and some sub-challenges remain entirely unsolved. Therefore, we have decided to keep the challenge open for another year! Improvements in downloads and scoring schemes will be made.
So stay tuned for updates...Read more
Emma Lundberg Director of the Human Cell Atlas, will present a keynote lecture on June 14th, entitled ”The Cell Atlas: A subcellular map of the human proteome” on the 32ndCongress of the International Society for Advancement of Cytometry in Boston, USA.
On this occassion, the CYTO Congress together with the Human Protein Atlas have organized a challenge for analysis of the images from the Cell Atlas, culminating in presentation of results in the final conference session, where participants will present their analytical methods and findings...Read more
In this week’s post, we will highlight proteins specifically expressed in a tissue with extensive plasticity - the female mammary glands. The evolutionary origin of mammary and milk gland-like structures is believed to date all the way back to 300 million years ago, and glandular secretory apocrine-like units in the skin of synapsids, an ancestor to mammals.
The mammary gland develops from the epidermis and is mainly composed of branched columnar and cuboidal epithelial cells that form distinct lobes...Read more
This month we take a closer look at the JAK family. The JAK – or Janus kinases, are intracellular proteins that transduce signals from cytokine receptors via the JAK-STAT pathway. More specifically the JAK family phosphorylates the receptor and thus activates downstream proteins, including transcription factors called STATs (Signal Transducers and Activators of Transcription). These transcription factors then migrate to the nucleus where they regulate transcription of many genes with diverse function, including cell growth, development and differentiation...Read more
Melanoma is a common form of cancer in the skin and among skin cancers it is the most deadly form. Melanoma originates from cells of melanocytic origin and most typically begins as a small intraepidermal tumor (melanoma in situ). As the tumor continues to grow and progress, tumor cells invade the epidermis and eventually spread to regional lymph nodes and subsequently via hematogenic spread to distant organs. Tumor thickness of the primary tumor is the most important determining prognostic factor and thus is early discovery of key importance for survival...Read more
Mathias Uhlen, Director of the Human Protein Atlas program, will present a keynote lecture on May 23 entitled "Tissue-based protein profiles – implications for human biology, drug development and precision medicine " on the 6th Pharmaceutical Science World Congress (PSWC 2017) in Stockholm, Sweden.
The focus of this year´s world congress will be " Future medicine for one world " including research and development related to systems approaches to drug discovery development and clinical usage...Read more
In a time when vast amounts of bioimaging data are produced in labs around the globe every day, effectively extracting salient information from this growing resource is paramount to understanding complex biological questions. In December 2016 the Cell Atlas was released, mapping the subcellular localization of over 12,000 human proteins and counting. As a part of this effort, gamers within EVE online and scientists in the HPA annotated the subcellular localization of each protein. This has created a massive high-quality atlas of microscopy images together with their subcellular protein localization annotations...Read more
The Cell Atlas database was just recently released with data on more than 12.000 proteins and mapping to 30 organelles. Today, the scientific findings are published in Science in "A subcellular map of the humanproteome".
The cell is a complex entity that carries out multiple functions. In order to do this, the different parts of the cells are organized in structures, called organelles. By investigating the organelles and its proteome, and to understand how the proteins vary over time and space we can truly begin to understand human biology on a detailed level...Read more
Today, you will be introduced to the master gland in the body - the pituitary gland.
The pituitary gland plays a crucial role in human physiology, and together with the hypothalamus this highly conserved and elegant system form a link between the nervous and endocrine system, by controlling the functions of the thyroid, adrenal glands, and the gonads, and also regulating growth, lactation, and water preservation.
The pituitary gland, also called hypophysis, consists of two separate lobes with dual embryonic origin; the anterior (adeno) pituitary gland originates from the oral cavity, and the posterior (neural) pituitary gland develops from the neural plate...Read more
This blog post is in honor of World Malaria Day
When infected mosquitos bite people they transmit parasites that causes malaria. Symptoms of malaria include fever and flu-like illness, and if left untreated the illness will cause anemia (loss of red blood cells) and eventually death.
According to WHO, malaria caused 429 000 deaths in 2015, and 70% of the deaths are children under the age of 5. Luckily, mortality rates are falling, and since 2010 the mortality has dropped with almost 1/3. Early diagnosis and treatment of malaria reduces deaths and prevents transmission. There are antimalaria drugs available, but currently, there is no availabe malaria vaccine...Read more
Today we highlight another part of Swedish or Scandinavian (food) culture - "Taco Fredag" or "Taco Friday". Doesn't sound Swedish to you? But staying in on a Friday night and having tacos with your family and/or friends is a thing here, and a big thing as it happens, with supermarkets having entire sections dedicated to this tradition.
So what other image to look at in this week's edition of the Human Protein Atlas blog than the one representing TACO1. TACO1 acts as a translational activator for the mitochondrial encoded cytochrome c oxidase 1, which is a component of complex IV of the mitochondrial respiratory complex...Read more
Today we meet yet another researcher within the Human Protein Atlas project, Johan Rockberg, Associate Professor in antibody technology and directed evolution at KTH - Royal Institute of Technology in Stockholm, Sweden. He is the group leader for the epitope mapping and therapeutic antibodies group within the Human Protein Atlas.
– I have a M. Sc in chemical engineering from KTH and University of Sydney and joined the Human Protein Atlas Project in 2003, right in the beginning. Since I took courses in computational and information science in parallel with chemical engineering it was natural to pursue a career in bioinformatics...Read more
A team from the Human Protein Atlas is attending the AACR Annual Meeting 2017 in Washington DC right now. This year, the meeting covers topics on research propelling cancer prevention and cures, and the Human Protein Atlas is represented by a booth where our team gives a personalized go-through of the Atlas to everyone who is interested in our open access resource. In addition, a demo version of a new Pathology Atlas can also be previewed in our booth. It will contain information on the prognostic genes and proteins for clinical outcome of the major cancer types in humans...Read more
It is Friday, and time for another image of the week, today from our Cancer Atlas group!
Renal cell cancer is a relatively common form of human cancer. Tumors develop in the kidney and have a tendency to grow into renal veins and metastasize to distant organs without the spread to regional lymph nodes as is common for many other tumor types. This particular case shows a papillary form of renal cell cancer that grows with papillary excrescences into cyst formations and with areas of necrosis.
This tumor has been stained with an antibody (HPA005785) that recognizes the CD44 protein...Read more
Today, we are back in the Tissue Atlas facilities at the Rudbeck lab in Uppsala. Borbala Katona and Maria Aronsson are research engineers in the group working with microscopy and annotation of stained tissues, which we described last week.
Borbala Katona has a bachelors degree in biomedicine and a masters degree in infectious medicine and has been working within the Human Protein Atlas since 2014.
Maria Aronsson has a masters degree in medical biology from Linköping University and joined the Human Protein Atlas in 2012...Read more
Welcome back to the Tissue Image of the Month.
This week we will focus on a complex and delicate tissue in our body, namely the retina!
More than a century ago, Cajal published his groundbreaking work on the retina. At that time, Cajal was eager to confirm previous observations he had made in other neural tissues, and he considered the retina very suitable to study due to its simple organization and structure.
The human retina is a multilayered neural tissue that originates from the developing brain, and populates the innermost layer of the eye, called the inner photosensitive layer...Read more
Today, we start a "mini-series" about our Tissue Atlas here at the blog. Join us on a tour through the lab, meet some of the people working there, and see some really nice images produced by the scientists.
All the work on our Tissue Atlas is done at our Uppsala site, with Cecilia Lindskog as site director. You can learn all about her in one of our previous blog posts.
First we meet research engineer IngMarie Olsson who is group leader for the Tissue Microarray Production, Immunohistochemistry, and Scanning-group...Read more
Researchers from the Human Protein Atlas are planning a clinical trial of a new treatment for nonalcoholic fatty liver disease and type 2 diabetes which harnesses liver cells own ability to burn accumulated fats.
In a study involving 86 patients with varying degrees of fatty liver disease, researchers found that the liver has the ability to burn up accumulated fats. The researchers propose a mixture of substances that will set this process in motion.
Assistant Professor Adil Mardinoglu says the team´s metabolic modeling approach, which relied on data from the Human Protein Atlas project, can be used for a number of chronic liver diseases...Read more
This week we highlight a new structure in the Cell Atlas available in version 16 thanks to the annotations done by citizen scientists in Project Discovery, a mini game within EVE Online. Rods & Rings.
As the name describes, these unique structures that form large rod and ring type aggregates in the cytoplasm that look a bit like sprinkles. Little is known about this structure and the proteins that are involved in it. In fact, it wasn't until 2011 when the term "Rods & Rings" was coined (Seeling HP et al. 2011,Carcamo WC et al. 2011)...Read more
A new research program has been started to produce all the human secreted proteins in mammalian cell factories. The program aims to facilitate studies of this important class of proteins involved in many human diseases.
The human secreted proteins, sometimes called the "secretome", consist of approximately 3000 proteins, which are produced inside our cells and then often transported out to the blood. This class of proteins is important in many central processes in humans, including bacterial and viral defense, inflammation, cell signaling and transport of nutrients...Read more
Today, it is time for the first image of the week from the Cancer Atlas!
Lung cancer is one of the deadliest and most common forms of human cancer. Different forms of lung cancer exist and non-small cell lung cancer is the most common form. The cancer image this week is selected from such a lung cancer that has been immunohistochemically stained for the proliferation marker Ki-67 (MKI67). Ki-67 is the most commonly used immunohistochemical marker in rutin cancer diagnostics. The Ki-67 antigen is expressed in all cell nuclei that are active in the cell cycle and thus positive staining in a tumor cell population reflects the level of proliferation in that particular cancer...Read more
This month, the online magazine Labiotech.eu writes about scientists who translates science from academia to the market. While there are a many academic entrepreneurial superstars in the US, Labiotech.eu points out that there are also some academic researchers in Europe that have been successful in taking their findings into the biotech industry and lists ten individuals in Europe who have been successful at co-founding biotech companies.
Out of these ten persons, no less than three have connections to Sweden. Emanuelle Charpentier, co-discoverer of CRISPR, did some of her findings at Umeå University...Read more
In 2017, February 28th will be the day that in Sweden is known as "Fettisdagen", (lit. "Fat Tuesday"), in other countries known as "Mardi Gras", "Faschingsdienstag" or "Shrove Tuesday". This day was originally celebrated in the Christian tradition as the last day of a three day feast to prepare for the forty day long fasting period before Easter. Today it has been popularized and in many places around the world this day is now known for its carnivals.
In Sweden together with some other northern European countries we like to eat "semlor" on Fat Tuesday...Read more
The term precision medicine describes the idea of providing effective treatment based on a patient´s molecular make up.
Eculizumab is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical haemolytic uremic syndrome (aHUS). However, eculizumab is a very expensive drug, and the treatment is not efficient for all patients...Read more
Tissue Atlas group is pleased to announce the launch of the Tissue Image of the Month. Previously, you have had the joy of experiencing interesting images of cellular organelles and proteins described by the Cell Atlas. Now we also hope that you will follow the blog posts and pictures of stained tissues with the same excitement and curiosity, as we dive into the world of histology, immunohistochemistry, cells and tissues.
First up - hairs and hair follicles.
Hair fibers consist of cells called trichocytes. The fibers vary in size, disposition and color due to factors such as age, sex, ethnicity and region of the body...Read more
In the latest version of the Human Protein Atlas, released in December 2016, the tissue atlas data is complemented with RNA-data from The Functional Annotation of Mammalian Genomes 5 (FANTOM5) project in RIKEN, Japan. The FANTOM data greatly overlaps with the Human Protein Atlas data, strengthening the results from both the projects.
The human genome consists of DNA which is transcribed into functional protein-coding transcripts (mRNA) and in turn is translated into proteins, the functional building-blocks of the cell. The entirety of mRNA molecules in a cell or tissue is called the "transcriptome"...Read more
Today we meet Hanna Tegel, site director at the AlbaNova site of the Human Protein Atlas, and group leader of the Antigen and Antibody Factory group. She has been with the Human Protein Atlas from the very beginning, and her career has evolved alongside the project.
– I took my M.Sc. in biotechnology at KTH – the Royal Institute of Technology here in Stockholm, and in the end of my education I complemented it with some physiology at the Karolinska Institute. As a part of this course I did a project at KTH, and when it was time for me to do my masters thesis I turned to the same professor. Now he was involved in the start-up of the Human Protein Atlas project...Read more
In a recent publication in Journal of Proteome Research, researchers from the Cell Profiling group of the Human Protein Atlas team present a new approach for validation of antibodies for bioimaging applications.
Antibodies are indispensible research tools, yet the scientific community has not adopted standardized procedures to validate their specificity. Here the researchers present a strategy to systematically validate antibodies for immunofluorescence applications using gene tagging.
Marie Skogs is the first author of the study.
– After a M. Sc...Read more
In two recent publications the group of Fredrik Pontén in Uppsala has identified two very strong, independent biomarkers for the prognostic stratification of breast cancer and renal cell carcinoma.
Renal cell carcinoma is the most common type of cancer affecting the kidney and there is an unmet clinical need for better prognostic and diagnostic tools for it. Diagnosis and subtyping of renal cell carcinoma are achieved through the morphological analysis of tumor sections. The application of immunohistochemistry can reveal important additional clues during the diagnostic work-up...Read more
During the Precision Medicine World Conference in Silicon Valley on January 23-25, Mathias Uhlen, leader of the Human Protein Atlas will give a talk about the recently initiated SCAPIS – SciLifeLab Wellness Profiling project.
The Precision Medicine World Conference is a conference series that attracts recognized leaders, top global researchers and medical professionals, and innovators across healthcare and biotechnology sectors to showcase practical content that helps close the knowledge gap between different sectors, thereby catalyzing cross-functional fertilization and collaboration...Read more
In a recent publication in Endocrinology, researchers from the Human Protein Atlas have performed a comprehensive analysis of the gene expression landscape of the adrenal glands to define genes with different degrees of "specific" expression compared to 31 other normal human organs and tissue types. The analysis showed that only 253 genes (approximately 1% of all putative protein coding genes) showed some level of adrenal gland specific expression pattern.
The adrenal gland is a composite endocrine organ with vital functions that include the synthesis and release of glucocorticoids and catecholamines...Read more
The year of 2016 is coming to an end. We have published 76 blog posts (77 with this one), on everything from Project Discovery to proteomics in narcolepsy, obesity and cancer, portraits of our researchers and of course several Images of the Week.
During the year we have released two new versions of the database, where RNA-seq data from the Genotype-Tissue Expression (GTEx) consortium from 28 different tissues with a corresponding tissue in the Human Protein Atlas have been included, and a new Cell Atlas with spatial location of more than 12,000 genes to 30 different organelles and cellular structures was launched...Read more
Over the last couple of months, you have hade the pleasure to see Image of the week here on the blog, where an image we find particularly interesting has been shown and discussed. Now that our Cell Atlas is out, you can browse images of your favorite protein directly in our database! In addition to all the images we have added, there are also new "Human Cell" chapters, which provide a knowledge-based analysis of the human cellular proteomes and an entry into the Human Protein Atlas from different perspectives...Read more
Yesterday our new Cell Atlas was released, at the American Society of Cell Biology Meeting. The Cell Atlas is an open-access interactive database with unparalleled high-resolution images. It visualizes for the first time the location of over 12,000 proteins in cells – opening the way to spatial proteomics, an exciting new discipline predicted to lead to a fundamental increase in our understanding of human health and disease.
Prof Mathias Uhlen, Director of the Human Protein Atlas explains:
– After the genome projects that has characterized the number of human protein-coding genes, the next step is to elucidate the function of these proteins...Read more
Over the last couple of weeks, readers of this blog have learnt about how we culture cells, and how we prepare them for microscopy. This week, the time has come to look into the actual imaging.
Martin Hjelmare is lab manager in the Cell Profiling group, and has worked within the Human Protein Atlas since 2007, the first couple of years in the protein factory, and since 2008 in the Cell Profiling group.
– In the protein factory I learnt a lot about basic lab routines; up scaling of protein expression, coupling columns, running gels, etc. This was very useful when I started working in the group of Emma Lundberg...Read more
To prepare all the images for the Cell Atlas, released on December 4, the cells used are primed for staining and microscopy. Sample preparation is an important step when performing immunofluorescence studies. If wrongly applied it can not only cause unsuccessful detection but also generate misleading information.
The sample preparation performed by the Cell Atlas team includes cell fixation, permeabilization, and immunostaining with primary and secondary antibodies.
– The fixation is the crucial step, and different fixation protocols work better for different sets of proteins, Christian Gnann, a research engineer in the Cell Profiling group explains...Read more
The Human Cell Atlas, to be released on December 4, displays high resolution, multicolour images of immunofluorescently stained cells. This provides spatial information on protein expression patterns on a fine cellular and subcellular level. From the start three cell lines, U-2 OS, A-431 and U-251 MG, originating from different human tissues were chosen to be included in the immunofluorescent analysis...Read more
In less than one month from now, we will release a new version of our database, HPA16! The biggest news is the introduction of a brand new Cell Atlas. It will be an image-based atlas over the subcellular distribution of the human proteome.
– Cells are the machinery of life. Much of the bustling activity in the human cell results from proteins performing specific tasks in designated compartments, the organelles. The Cell Atlas that we are creating will be image-based and describe the subcellular distribution of the human proteome, says Emma Lundberg, Director of the Cell Atlas...Read more
In a recent study in Journal of Proteome Research by Human Protein Atlas-researchers a new reactive epitope of a prostate specific protein, particularly reactive in the late stages of prostate cancer is identified.
According to WHO, prostate cancer is the second most incident cancer in men and the fifth leading cause of death in men worldwide, and there is a demand for novel targets and approaches to diagnose and treat this cancer type. Five-year survival is reached by almost 100% of patients if the disease is still at a local and regional stage; however, the survival rate drops down to 30% in the case of aggressive form with distant metastasis and relapse after treatment...Read more
This week we look at a very spooky protein, BAT3 which localizes to the nucleoplasm (looks like jack o'lanterns if you squint hard enough) and cytoplasm of the cell as seen in Figure 1 in A-431 cells.
In addition to having a spooky name, this protein, also known as BAG6, was first identified as being involved in programmed cell death (apoptosis). Subsequent studies have revealed that BAT3 plays a role in many important cellular processes including gene regulation, protein synthesis, protein quality control, and protein degradation (Binici J & Koch J. 2014)...Read more
Several previous reports have concluded that RNA levels cannot be used to predict protein levels. However, in a new study from KTH Royal Institute of Technology, published in the journal Molecular Systems Biology scientists from the Human Protein Atlas show that protein levels can be predicted from RNA levels if a gene-specific RNA-to-protein factor is used.
The human genome consists of DNA, a molecule that contains the instructions needed to build and maintain cells. For the instructions to be carried out, DNA must be read and transcribed into RNA transcripts that can be used to produce protein. The transcriptome is a collection of all the transcripts present in a cell...Read more
It's time for another HPA image of the week! This week we would like to tease an annotation that is not yet publicly available, but is coming soon in the December 4 release of the Cell Atlas.
During the cell cycle, each chromosome containing your DNA replicates. During mitosis, each chromosome lines up with its copy in the middle of the cell. At this point, the copies of each chromosome are pulled apart from each other via a structure called the mitotic spindle. In order for this chromosomal separation to happen correctly, the two copies of each chromosome must be attached to the microtubules via the kinetochore ( DeLuca J.G. et al 2002)...Read more
In a recent study, published in Blood, researchers have used affinity reagents from the Human Protein Atlas project to analyze plasma samples to identify candidate protein markers associated with risk of venous thromboembolism.
Venous thromboembolism is the third most common cardiovascular disease and a leading cause of death and disability worldwide. Complex interactions between genetic, environmental and acquired risk factors underlie disease development. The first step in the process of developing clinically applicable predictive tools is the identification of novel markers that associate with the disease...Read more
In a recent publication in Cell Systems researchers have identified endothelial biomarkers that provide potential vascular drug targets and candidates for functional studies to increase understanding of the endothelium in health and disease.
Endothelial cells line the inside of all vessels and have a critical role in the regulation of hemostasis, inflammation, defense against blood borne pathogens, vascular tone, angiogenesis, and the transport of molecules and nutrients to and from the blood stream.
Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds...Read more
This week the 2016 Nobel Prize in Physiology or Medicine was announced and has been awarded to Yoshinori Ohsumi for his work in with understanding autophagy. Congratulations to Dr. Ohsumi on his well deserved award! Please read the link above for a great and brief explanation of Dr. Ohsumi's contributions and other important discoveries related to autophagy.
This week we highlight DNA damage regulated autophagy modulator 2 (DRAM2), a well known inhibitor of autophagy. Figure 1 shows an example of DRAM2 in U2 OS human osteosarcoma cells...Read more
The Human Protein Atlas has since the first array validated antibody in November 2004 now passed 50 000 protein microarray validated antibodies.
The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data. For the protein data, antibodies are used to show localization, and now 50 000 antibodies have been produced and verified within the project.
– This is a true heroic effort, says professor Peter Nilsson, site director at the SciLifeLab-site in Stockholm...Read more
In a recent study published in Proteomics Clinical Applications researchers from the Human Protein Atlas have profiled 280 brain-enriched proteins in cerebrospinal fluid from patients with Alzheimer´s disease, Parkinson´s disease and dementia with Lewy bodies. This study is part of a larger effort aiming to expand the knowledge of brain-enriched proteins in human cerebrospinal fluid and to provide novel insight into the relation between such proteins and different neurodegenerative diseases.
The researchers report a multiplexed protein profiling using an affinity-based proteomics approach to generate cerebrospinal fluid profiles of brain-enriched proteins...Read more
As it's Mitochondrial Disease Awareness Week, I know you have all been thinking about mitochondria all week. And you should! They are very important organelles.
Your mitochondria are responsible for much of the energy production in your cells. Perhaps the most interesting thing about mitochondria is that they have their own DNA which means some proteins in the mitochondria come from nuclear DNA and some from mitochondrial DNA. In a previous image of the week we highlighted TOMM5, a protein responsible for transport of nuclear encoded mitochondrial proteins into the mitochondria...Read more
This week, it is Mitochondrial Disease Awareness Week. Therefore we would like to take the opportunity to talk about the mitochondrial proteome, the work we do within this field, and you will even get to meet one of our researchers, involved in this work.
The mitochondria are distributed throughout the cytoplasm of the cell, each organelle enclosed by a double membrane, the inner one forming the characteristic folds known as cristae. Mitochondria are essential for producing the cell´s need of ATP through cellular respiration, but have also been shown to participate in many other cellular functions, including apoptosis, calcium storage and cellular signaling...Read more
Welcome to another HPA image of the week! This week we take a look at another member of the vesicle family, the lysosomes.
In a way, lysosomes can be thought of as the recycling plants of your cells. Lysosomes are small membrane bound vesicular organelles that degrade biomolecules within your cells so that the materials in these molecules can be recycled and used for other cellular processes. Often these biomolecules come from vesicles known as endosomes that bring in materials from outside your cells, however lysosomes are also known to degrade other organelles, and products from within the cell...Read more
In an article in a special edition of Proteomics, on protein arrays researchers from the Human Protein Atlas describe the development of a novel assay concept, which combines the flexibility and multiplexing capacity of single-binder assays and the specificity and sensitivity aspects of dual-binder assays. They developed a multiplexed dual-binder assay procedure, which is based on a sequential protein capture.
– This assay is a great addition to the antibody-array toolbox of the Biobank Profiling Group, both to support related assay development activities and for biomarker discovery applications, says Burcu Ayoglu, first author of the study...Read more
This week's image of the week shows an example for the growing number of organelles that we annotate in the Cell Atlas. Lipid droplet (LD) proteins fall under the vesicle category, but starting with version 16, they will have their own place in the Atlas? organelle panel.
LDs can be found in animals, plants, fungi and even some bacteria have them. They have a simple and evolutionary conserved structure: A hydrophobic core that contains the lipids is surrounded by a phospholipid monolayer with proteins attached. This phospholipid monolayer makes the LDs unique among organelles; all other membranes consist of a double layer...Read more
An international working group has formulated directives to evaluate antibodies used in biomedical research. A paper in Nature Methods suggests five conceptual pillars for antibody validation.
Antibodies are used frequently both in research and in the clinic, and today over two million commercial antibodies are available for the analysis of human proteins. This has been accompanied with a dramatic development in clinical treatment of diseases, like cancer and autoimmune diseases, where biological drugs in the form of antibodies have changed the treatment of many patient categories...Read more
Welcome back blog fans! After a brief hiatus the image of the week highlights from the HPA are back! This week we are discussing the Endoplasmic reticulum, which is not just difficult to say, but is where many of your proteins are made.
The endoplasmic reticulum (ER) is one of the largest organelles in the cell. It is a delicate membranous network composed of sheets and tubules that spreads throughout the whole cytoplasm and is actually contiguous to the nuclear membrane. Two major forms of the ER can be distinguished: the rough ER and the smooth ER. Both have different functions...Read more
Adil Mardinoglu is a SciLifeLab fellow and the newest addition to the Protein Atlas team of principal investigators. He is the leader of the systems biology group, a group that create biological networks to identify drug targets and discover biomarkers for the development of efficient treatment strategies.
But Adil´s background is not in medicine, he is an electronic engineer with a PhD in computational biology.
– I did my PhD in Ireland where I worked with magnetic drug targeting, he says.
After a one year post doc doing research on neuronal networks, Adil Mardinoglu moved to Chalmers in Gothenburg to join Jens Nielsens group in systems biology...Read more
In a recent publication in Nucleic Acids Research, researchers from the Systems Biology group at the Human Protein Atlas investigated anomalies in regulation of lipid metabolism in the liver, in association with hepatocellular carcinoma.
Hepatocellular carcinoma has a high mortality rate and early detection of the disease is crucial for the application of effective treatment strategies. Several lines of evidence imply that lipid anomalies underlie the hepatocellular carcinoma pathogenesis.
Here, the researchers applied a tailored network-based approach to identify signaling hubs associated with regulation of this part of the metabolism...Read more
In a paper published in Nature Scientific Reports last week, researchers from the Human Protein Atlas describe a method for stratification of responders towards the drug eculizumab that allows for precision medicine and should be applicable to several other diseases and therapeutics.
The term precision medicine describes the idea of providing effective treatment based on a patient´s molecular make up. Recent advances in molecular diagnostic tools and handling of large data sets allow for the stratification of patients based on e.g. genetic or protein information and make it possible to provide tailored treatment for these sub-groups...Read more
This week, the image of the week highlights the Golgi apparatus. This week's contribution is brought to us by Peter Thul, a postdoctoral researcher who works on the Subcellular protein atlas, and specializes in understanding secretory pathway.
The Golgi apparatus was discovered by the Italian physician and scientist Camillo Golgi, who discovered the fine membraneous structure in 1898 (Mazzarello P., Garbarino C., & Calligaro A. 2009). Since then it has frequently drawn the attention of researcher because of its prominent role in the secretory pathway of cells.
The secretory pathway describes the route that proteins take to get to the outside of the cell...Read more
Cancer can be defined as a common heterogeneous and potentially deadly disease that affects approximately 1/3 of the human population. The common denominator for cancer is the development of an uncontrolled growth of cells that eventually leads to multiple organ failure and death.
The cancer proteome is based on genes that are implicated in cancer. Expression of these genes in normal cells contributes to normal growth, survival and function, whereas dysregulated expression, including overexpression, loss of expression or expression of a defect protein in cancer cells contributes to ungoverned tumor growth...Read more
Though frequently overlooked as being a "catch-all" for proteins that don't reside within another organelle, cytoplasmic proteins are anything but.
One important role of proteins in the cytoplasm is the regulation of gene expression. There are two main ways in which gene expression is regulated; when converting the genetic code in your DNA to RNA (transcription), and when converting RNA to proteins (translation). Though transcription (DNA to RNA) occurs in the nucleus, cytoplasmic proteins are often involved in activating transcription factors which then move to the nucleus to perform transcription.
The protein stained in Fig 1...Read more
In a paper in a recent issue of Cell Metabolism, Human Protein Atlas-researchers investigate the biological processes that are altered in obese subjects.
Obesity is associated with an increased risk for a wide range of morbidities, including insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Although the prevalence of obesity continues to dramatically increase worldwide, a clear understanding of the underlying molecular mechanisms involved in the progression of associated disorders is still lacking...Read more
In a recent number of Nature Reviews, Human Protein Atlas researchers Mathias Uhlén and Adil Mardinoglu discuss a study by E.G. Williams and co workers in Science where five complementary -omics datasets across various environmental states (including genomics, transcriptomics, proteomics, metabolomics and phenomics) using the liver as a platform for multiomics analysis are integrated...Read more
This week, image of the week highlights another organelle, the nucleoli fibrillar center!! This week's contribution is brought to us by Lovisa Åkesson, who works on the Subcellular protein atlas, and specializes in understanding nuclear function.
A few months ago, an excellent example of a protein located in the nucleoli rim was shown in another blog post. Today, we are diving deeper into the function of the nucleoli and specifically the fibrillar center, another nucleolar compartment.
As mentioned before, the nucleolus is a non-membrane bound structure located within the nucleus and there is usually more than one in each nucleus...Read more
Today we meet yet another researcher within the Human Protein Atlas project, Jochen Schwenk, Associate Professor for Translational Proteomics at KTH - Royal Institute of Technology in Stockholm, Sweden. He is Director of the Biobank Profiling facility at the Science for Life Laboratory and a Principal Investigator within the Human Protein Atlas and the KTH Center for Applied Proteomics.
– I have a PhD in Biochemistry from the University of Tübingen in Germany, and when I saw presentations from the Human Protein Atlas Director Mathias Uhlén at a few meetings I thought that this would be an exiting project to work with after my PhD thesis, Jochen Schwenk says...Read more
It's time for another HPA image of the week! This week we interrupt our series of organelle highlights to bring you another great image brought to us by the citizen scientists in Project Discovery, and specifically by x Truf a member of the Signal Cartel in EVE online who found this image while playing Project Discovery. This is x Truf's second contribution to our image of the week, and we'd like to give special thanks for these contributions!
The protein stained in Fig 1. is an image of Torsin A interacting protein 1 (TOR1AIP1, also known as LAP1). This staining shows signal specific to both the nuclear membrane and microtubules...Read more
In a recent publication in JCI Insight researchers from the Human Protein Atlas have described the expression of the currently known cancer-testis antigens (CTAs) in non-small cell lung cancer, and have added 50 new CTAs to this list.
Lung cancer is the most common cause of cancer related death in Sweden and worldwide. Most patient present with advanced disease and have a short life expectancy despite modern therapy.
Dijana Djureinovic is a PhD student in the group of Cecilia Lindskog at Science for Life Laboratory. She started her PhD studies two years ago, but worked in the project before that, on antibody validation...Read more
Let's have a look at another fascinating compartment of the cell, the centrosome! Located in close proximity to the nucleus, the centrosome is so small that it sometimes suffers from being overlooked. However, despite its humble size it is a very important organelle with great impact on cellular function.
The centrosome was first described in 1888 and has been a very popular organelle to study among biology researchers ever since (Conduit P.T. 2015). The most well characterized function of the centrosome is to serve as the organizing center for the microtubules that build up the internal architecture of the cell, the so-called cytoskeleton...Read more
Secreted and membrane-bound proteins are important for physiological processes and are potential drug targets as they are easily accessible in the extracellular space and provide a gateway to the intracellular environment. About 3,000 protein-coding genes are predicted members of the secretome; examples of secreted proteins are cytokines, coagulation factors, hormones, and growth factors. Important members of the membrane proteome, consisting of about 5,500 genes encoding predicted membrane-bound proteins, are ion channels of molecular transporters, enzymes, receptors, and anchors for other proteins.
A majority of the human genes encode several splice variants...Read more
It's time for another Image of the week! This week's image is brought to us by Diana Mahdessian, who works on the Subcellular protein atlas, and highlights cell division and various stages of mitosis. In previous blogs we have discussed the importance of certain proteins in the cell cycle including dividing centrosomes and FDXR in mitochondria.
The cell cycle is an ordered series of events that ultimately leads to the division of the "mother" cell into two "daughter" cells (cells are given feminine names because they are capable of reproducing).
The cell cycle consists of three distinct phases; interphase, mitosis and cytokinesis...Read more
A large number of proteins are needed in all cells throughout the human body. These proteins are sometimes called housekeeping proteins, suggesting that their expression is crucial for the maintenance of basic functionality of all normally functioning cells.
A transcriptomics analysis shows that about 9,000 genes are expressed in all tissues and are therefore expected to fulfill these tasks, such as gene expression, metabolism, and cell structure.
As for gene expression, it is easily understood that every cell must have proteins that are involved in the genetic machinery of translating DNA to functional proteins, like RNA polymerases and ribosomal proteins...Read more
Welcome back to HPA image of the week! This week we highlight another organelle brought to us by Mikaela Wiking aka HPA_Illuminator, the intermediate filaments!
Intermediate filaments are one of the three cytoskeletons of the cell, together with actin filaments and microtubules.
The expression of intermediate filaments can be extremely dependent on cell type, for example the intermediate filament protein group keratins, discussed in a previous IOTW, are key components in hair, nails and skin...Read more
In January 2015, the Tissue-based map of the human proteome by Uhlén et al was published. According to Google Scholar, the paper already has more than 400 citations. In a recent editorial by Cecilia Lindskog, the potential utility of the Human Protein Atlas and the Tissue-based map is reviewed.
Cecilia Lindskog is site director of the Tissue Atlas, and you can read more about her and the Tissue Atlas in this blog post from May this year...Read more
Welcome back to Image of The Week! We will be periodically highlighting an organelle in the coming image of the week posts, written by members of the Subcellular Human Protein Atlas project. This week we kick things off with a post by HPA_Illuminator, and what better way to start than with the mitochondria, the (true) powerhouse of the cell!!!
Mitochondria are found in almost all human cells, in varying numbers. They are known as the powerhouse of the cell as they are responsible for producing the majority of the energy in your body (in the form of ATP, adenosine triphosphate)...Read more
In a very recent study, published in Respiratory Research, researchers from the Human Protein Atlas and Karolinska Institutet performed protein profiling of broncho-alveolar lavage (BAL)-fluid and serum using an antibody suspension bead array technology with the aim to find proteins associated to sarcoidosis.
Sarcoidosis is a granulomatous systemic inflammatory disease in which more than 90 % of all patients develop pulmonary manifestations. Several gene associations have previously been described, but established and clinically useful biomarkers are still absent...Read more
Welcome to HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by solartech0 who found this image while playing Project Discovery in EVE online.
The protein stained in Fig 1. is an image of ferredoxin reductase (FDXR) found in the mitochondria of the cell. This sample shows a staining of FDXR in A549 adenocarcinomic alveolar basal epithelial cells.
FDXR is a protein involved in cellular metabolism. This process is what provides energy for our cells and is carried out in the mitochondria of the cell...Read more
Last week, researchers from the Human Protein Atlas, together with others, published a study on drug-induced liver injury in the journal Liver International.
Drug-induced liver injury is the single leading cause for termination of drug development and safety-related withdrawal of approved drugs from the market. In clinical practice, it accounts for more than 50% of liver failure cases and represents a major safety issue for patients. In some patients, drug-induced liver injury can cause severe injury leading to acute liver failure that can be life threatening and require liver transplantation...Read more
It's time for another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by x Truf a member of the Signal Cartel in EVE online who found this image while playing Project Discovery.
The protein stained in Fig 1. is an image of Moesin (MSN) found in the plasma membrane of the cell. This sample shows a staining of MSN in U-251 MG human glioblastoma astrocytoma (brain) cells.
MSN is a member of the ERM family which provide a link between plasma membranes and actin filaments. This link was briefly discussed in a previous blog...Read more
A new study by researchers within the Human Protein Atlas project was just published in Autoimmunity .
The researchers analyzed the presence of autoantibodies in patients with vaccine-associated narcolepsy. In an initial screening, IgG reactivity to approximately 10000 protein fragments was investigated, revealing a large heterogeneity in which autoantibodies that are present in different individuals.
Anna Häggmark is the first author of the paper...Read more
Welcome to another HPA image of the week! This week we take a look at vesicles and another type of data present in the HPA.
The protein stained in Fig 1. is an image of RAB5C. This protein is found in vesicles and specifically, in lysosomes of the cell. This sample shows HeLa human cervical adenocarcinoma cells.
These cells are actually transgenic and made to express green fluorescent protein on the RAB5C protein (RAB5Cgfp). This is a method we use to check the validity of our antibodies...Read more
In a recent publication in European Journal of Allergy and Clinical Immunology, researchers use an affinity proteomics approach to analyze plasma profiles of a 362 proteins in 154 children with persistent or intermittent asthma and controls. To this end, antibody suspension bead arrays developed within the Human Protein Atlas was used.
Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. Asthma affects approximately 300 million people worldwide and is characterized by bronchial hyperresponsiveness and reversible expiratory airflow limitation...Read more
Welcome to another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Shiverwarp who found this image while playing Project Discovery in EVE online.
The protein stained in Fig 1. is an image of Coronin, actin binding protein, 2B (CORO2B) found in the focal adhesions and at the plasma membrane of the cell. This sample shows U-251 MG human glioblastoma astrocytoma (brain) cells.
Focal adhesions are transmembrane groups of protein that allow the cell to "grab" the surrounding environment...Read more
Time has come for the second interview with a researcher within the Human Protein Atlas project. Today we meet Cecilia Lindskog, site director of the Tissue Atlas.
– I have a Master of Science in Biomedicine and a Doctor of Philosophy in pathology from the Faculty of Medicine, Uppsala University. I joined the Human Protein Atlas project in 2006, and also have industry experience in the biotechnology industry, from Oncomark Ltd, Dublin, Ireland.
Cecilia Lindskog´s main research interests have always been understanding the biology and functions of different organs, and the underlying mechanisms leading to cancer and other diseases...Read more
Welcome to another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Selphentine who pointed out several nice examples of proteins localized to "nuclear speckles". In Project Discovery, citizen scientists are refining our annotations for proteins within the nucleus by labeling these nuclear speckles, previously not annotated in the atlas.
The protein stained in Fig 1. is an image of DEAD (Asp-Glu-Ala-Asp) box polypeptide 39B (DDX39B) seen in the nuclear speckles. This sample shows MCF-7 cells, a human adenocarcinoma cell line from breast cancer...Read more
In a very recent paper in Journal of Histochemistry and Cytochemistry , with researchers from the Human Protein Atlas, it is shown that the expression of aquaporin 9 is limited in normal tissues, and high membranous expression is observed only in hepatocytes.
Aquaporin 9 is known to facilitate hepatocyte glycerol uptake. Murine aquaporin 9 protein expression has been verified in liver, skin, epididymis, epidermis and neuronal cells using knockout mice.
One goal of the current study was to systematically explore the distribution of aquaporin 9 expression in humans...Read more
This week HPA image of the week, I've decided to highlight two of my favorite things, the cell cycle and actin filaments!
The protein labeled in Fig 1. is an image of Cell division cycle 42 effector protein (Rho GTPase binding) 4 (CDC42EP4). In addition to being quite a mouthful, this protein resides in the cytoplasm and is associated with the actin filaments. In this image, CDC42EP4 is seen in U-2 OS human osteosarcoma cells.
As the name suggests, the CDC42EP4 is a protein associated with CDC42, which helps regulate the transition from G1 to S (in which DNA is replicated), and is essential for proper cell cycle progression (Yasuda S et al. 2006)...Read more
As a follow up from last week´s blog post, on Jan Mulder and his work, we now present the most recent publication from his lab, on the anatomical distribution of neuronal calcium-binding proteins 1 and 2 (NECAB1/2) in rodent and human spinal cord.
Mingdong Zhang is the first author of the study and a PhD student registered in the Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics (MBB) at Karolinska Institutet.
– But much of my actual work is carried out in the Department of Neuroscience...Read more
This week, the Human Protein Atlas is highlighting a new atlas recently released in HPA 14, The Mouse Brain Atlas. This image from The Mouse Brain Atlas was brought to us by Nadya Petseva, a team member on the project. I know what you're thinking, what's a mouse doing in the "human" protein atlas?!
Though we typically deal with human cells and tissues in the HPA, it is not currently possible to image full human brain at the cellular level, whereas using a mouse brain we can gain key insights into how proteins in the brain function in situ. This makes mice an attractive "model organism" as their brains actually consist of very similar regions to those found in humans...Read more
Today we introduce a new feature on the Human Protein Atlas blog, interviews with scientists involved in the project. First out is Jan Mulder, head of the brain initiative.
– I am a biologist, specialized in neurobiology with a PhD in molecular neurobiology from Rijksuniversiteit Groningen, The Netherlands.
In 2004, at the same time that the Human Protein Atlas project was producing its first antibodies, Jan Mulder came as a post-doc to the group of Tomas Hökfeld at Karolinska Institute. In collaboration with Mathias Uhlén and the Human Protein Atlas he began to explore the possibilities to use antibodies raised against human targets on rodent brain tissue...Read more
It's the end of the week, and that means another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Aleksandra Shaishi who found this image playing Project Discovery.
The protein labeled in Fig 1. is an image of the antibody HPA006539, which labels solute carrier family 2 (facilitated glucose transporter) (SLC2A) member 3 and member 14. This is what we call a "multi-targeting" antibody as it binds more than one protein...Read more
In the Human Protein Atlas, there are 32 human organs and tissues analyzed. 2489 of the genes have significantly higher expression in one tissue compared to all other tissue types. Analysis show that testis is the organ with the largest number of tissue-enriched genes, with 1057 genes classified as testis enriched. The specific events and alterations of cell structure during spermatogenesis, and the fact that sperm has the ability to survive outside the male body may explain why testis has the largest number of enriched genes.
The organ with the second highest number of enriched genes is the brain with 381 enriched genes...Read more
It's time for another HPA image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Altytwo Altryness who found this image playing Project Discovery and correctly identified the antibody as labeling intermediate filaments and displaying cell to cell variability.
The protein labeled in Fig 1. is an image of keratin 6B, type II (KRT6B) in U-2 OS cells, human epithelial osteosarcoma, which is the reference cell line for the HPA.
Keratin is a well known intermediate filament protein that form filaments roughly 10nm in diameter...Read more
Today, a new version, number 15, of The Human Protein Atlas is launched that includes extensive transcriptomics data and a new display view to allow comparisons of human tissue profiles on both the RNA and protein level. In this new version it is possible to do comparisons of primary data from several sources, including external efforts such as the GTEx dataset generated from the Broad Institute in Boston, US.
The GTEx dataset includes more than 1600 postmortem samples from mostly overlapping, but in some cases unique, tissues compared to the Human Protein Atlas consortium...Read more
It's time for another Image of the week! This week's image was brought to us by citizen scientists in Project Discovery, and specifically by Yadaryon who pointed out several nice examples of proteins localized to the rim of the nucleoli.
The nucleolus is an organelle within the nucleus of your cells. There may be one or more nucleoli in each nucleus, but they usually occur in small numbers. The primary job of the nucleoli is to assemble ribosomes which in turn make proteins within your cells...Read more
To understand the molecular functions of the urinary bladder, researchers including scientists from The Human Protein Atlas project have recently defined the expression of elevated genes in the bladder.
The main function of the urinary bladder is to store the urine made by the kidneys, allowing urination voluntarily. The urothelium also plays an important role in preventing rupture of urine storage and leakage of toxic urinary substances into the blood...Read more
Welcome to the second edition of image of the week. This week's image was brought to us by citizen scientists in Project Discovery. After analyzing the recent data from the project, this image was among the most frequently labeled as "abnormal" by the users.
This is an image of EPB41L1 (erythrocyte membrane protein band 4.1-like 1). This staining is observed in HEP G2 human liver hepatocellular carcinoma cells. As you can clearly see here, there is significant cell-to-cell variation (CCD) in the staining, and even within a single cell at times.
As the name suggests, this is a well known membrane protein...Read more