THE HUMAN PROTEIN ATLAS BLOG
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
In a recent study, scientists including members of The Human Protein Atlas project have identified the beta cell specific protein GPR44 as a potentially novel tool for measuring beta cell mass in vivo, using radiolabeled PET ligands targeting GPR44.
The pancreatic beta cell is responsible for producing insulin and beta cell loss is one of the causes underlying diabetes. Blood biomarkers to measure beta cell function exist, but there is a lack of good tools for measuring the beta cell mass inside the body.
In this study, the ligand targeting GPR44 was compared to a ligand targeting the established beta cell marker VMAT2, and the performance was evaluated...Read more
Introducing the HPA image of the week! Each week we will pick an image we find particularly interesting and briefly discuss it. This series will particularly focus on images brought to us by citizen scientists working on Project Discovery, though may include images from other projects in the atlas as well.
This week's image is brought to us by citizen scientist CalebAyrania who found this staining playing Project Discovery and correctly identified the antibody as labeling centrosomes in mitotic cells (cells undergoing division). This staining was observed in CACO-2 colorectal epithelial adenocarcinoma cells...Read more
In a recent study by co-workers of The Human Protein Atlas project over 100 genes with elevated expression pattern in the normal endometrium was found. A majority of these genes are well-known and have been extensively characterized. However, the list of endometrium-specific genes also includes uncharacterized genes, providing starting points for further studies of their role in normal homeostasis and diseases affecting the endometrium.
The uterus contains the endometrial mucosa which is the site for embryo implantation...Read more
Thanks Science Fans!
The response to Project Discovery has been amazing and overwhelming. You have taken to the game in a way none of us expected. Keep it up!
First, in an effort to stream line our interactions with you we have created a number of official social media outlets:
EVE forums: We have a number of official accounts we will respond to questions with.Twitter: HPA_Discovery - dedicated to posting updates, announcements and all things Project Discovery. Twitter is severely character limited so it's difficult to answer questions there.Reddits: /r/EVE and /r/projectdiscovery - We will be here for support as well...Read more
The proteins are the building blocks of life
The human body is built of organs and tissues, each organ and tissue constitute of groups of cells, and each cell is built from a set of proteins - the building blocks of life.
In total, the human body consists of 100 billion cells, in every cell the genetic code translate to a set of proteins that will give the cell its specific properties.
Our mission is to map all proteins in the human body to better understand health and disease.
In order to identify the subcellular localization of proteins in cells, millions of images have been taken within the Human Protein Atlas project...Read more
The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling
In a recent study by scientists from the Human Protein Atlas project and colleagues, a genome-wide transcriptomics analysis combined with immunohistochemistry-based protein profiling was performed to describe the gene and protein expression patterns that define the human gastrointestinal tract (GIT).
The GIT organs (stomach, duodenum, jejunum/ileum and colon) were compared to gene expression levels in 23 other normal human tissues...Read more
Loss of ASRGL1 expression is an independent biomarker for disease-specific survival in endometrioid endometrial carcinoma
The ASRGL1 protein is a novel, powerful, and independent biomarker for prognosis in endometrial carcinoma.
In a recent study by scientists from the Human Protein Atlas project and collaborators at the University of Bergen and University of Turku, the l-asparaginase (ASRGL1) protein was identified as an endometrial carcinoma biomarker candidate by searches in the HPA-database.
ASRGL1 expression was immunohistochemically evaluated on two large independent endometrial carcinoma cohorts using an extensively validated antibody...Read more
The human skin-specific genes defined by transcriptomics and antibody-based profiling
Normal skin is consists mainly of epidermal cells in different phases of de-differentiation (keratinization) organized in several distinct layers with different appearance, functions, and molecular signatures. To characterize the skin-specific genes and the landscape of gene and protein expression in normal human skin in different layers and stages of differentiation, scientists from the Human Protein Atlas project have combined immunohistochemistry-based protein profiling and genome-wide deep sequencing of mRNA to compare skin with other normal tissue types...Read more
Novel biomarkers for prostate cancer found while defining the prostate specific transcriptome and proteomeTo better understand the function of the prostate and diseases associated with it, it is important to explore the molecular constituents that make up the prostate gland.
In a recent study by scientists from the Human Protein Atlas project and colleagues both gene and protein expression profiles were investigated in prostate tissue and compared to 26 other human tissues. The aim was to identify potential prostate specific biomarkers for potential clinical use...Read more
Systematic antibody validation with siRNA for the Human Protein Atlas
Antibodies are among the most frequently used tools for basic research and clinical assays. For antibodies used in therapy or diagnostics, there are well-defined and strict guidelines that must be complied with before approval for clinical assays. For research antibodies, such guidelines have not yet been developed, despite the importance of demonstrating that they are specific, selective, and yield reproducible results in the immunoassay for which they are to be used...Read more
Presenter: Tove Alm
Presentation: The Human Protein Atlas: a flagship resource for understanding the whole human proteome
ELIXIR Europe Conference Open Data in Action: Life Science Data Infrastructure for Innovation
Presenter: Emma Lundberg
Presentation: Closing plenary: Characterizing human organelle proteomes - Towards a complete Cell Atlas
21st Annual Lorne Proteomics Symposium..Read more
Exploration of high-density protein microarrays for antibody validation and autoimmunity profiling
Protein fragments are used within the Human Protein Atlas project for the generation of antibodies, these fragments have also been utilized for the validation of the antibodies on antigen microarrays.
All antibodies produced by the Human Protein Atlas have been validated for target recognition on antigen microarrays comprising of their target antigen and 383 other protein fragments. In total over 42.000 protein fragments have been arranged in sets of 384...Read more
Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model
From primary to malignant - what changes? Bridging transcriptomics and proteomics to reveal the molecular changes during malignant transformation in a four-step cancer cell line model
In order to find out more about the changes that occur when a primary cell is transformed into an aggressive cancer cell, integration of biological information has proven to be successful. By bridging transcriptomics and antibody based proteomics data we showed how the major changes during malignant transformation could be scrutinized...Read more
Proteomic Profiling Reveals Autoimmune Targets in Sarcoidosis
Sarcoidosis is an inflammatory lung disease with unknown cause. Previous research has shown that sarcoidosis patients have generally higher levels of antibodies compared to healthy controls but so far the role and protein targets of these antibodies are not well understood.
In this study we used protein microarrays to investigate autoantibody targets in bronchoalveolar lavage (BAL) fluid in the search for autoantigens associated to disease...Read more