Friedrich Miescher Research Articles

Immunocytochemical Detection of Integrins α3 and β1 in Allografts of the Marine Sponge, Microciona prolifera.

Previous articleNext article No AccessCellular BiologyImmunocytochemical Detection of Integrins α3 and β1 in Allografts of the Marine Sponge, Microciona proliferaClarissa A. Sabella, Ellen E. Faszewski, Jane C. Kaltenbach, William J. Kuhns, Max M. Burger, and Xavier Fernandez-BusquetsClarissa A. Sabella1. Mount Holyoke College, South Hadley, Massachusetts Search for more articles by this author , Ellen E. Faszewski2. Wheelock College, Boston, Massachusetts Search for more articles by this author , Jane C. Kaltenbach1. Mount Holyoke College, South Hadley, Massachusetts Search for more articles by this author , William J. Kuhns3. Hospital for Sick Children, Toronto, Canada Search for more articles by this author , Max M. Burger4. Friedrich Miescher Institute, Basel, Switzerland Search for more articles by this author , and Xavier Fernandez-Busquets5. University of Barcelona, Barcelona, Spain Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Biological Bulletin Volume 207, Number 2October 2004 Published in association with the Marine Biological Laboratory Article DOIhttps://doi.org/10.1086/BBLv207n2p162 Views: 31Total views on this site PDF download Crossref reports no articles citing this article.

Rags before the riches: Friedrich Miescher and the discovery of DNA.

Like many success stories, the career of DNA as the molecule of heredity and icon of modern biology began under somewhat less glamorous circumstances. The story begins in 1844, one hundred years before Avery and his colleagues realised the significance of DNA as the genetic material (see accompanying article), with the birth in Basel of Friedrich Miescher, who went on to discover DNA at the age of 25.Following a family tradition, Miescher trained as a doctor, but chose not to become a clinician – in part because of a hearing impairment. Instead, he went to Tubingen in 1868 and joined the lab of Felix Hoppe-Seyler, one of the pioneers of biochemistry, who had discovered hemoglobin just a few years before. At the time, the chemical characterisation of cellular contents was seen as a new and exciting possibility to understand the phenomena of cell growth and multiplication. The importance of these processes had been realised through microscopical observation, but what drove them or how they were controlled was totally enigmatic.View Large Image | View Hi-Res Image | Download PowerPoint SlideAs his pet cell for investigation, Miescher chose white blood cells, because they occurred as individual cells and were easy to obtain. Discarded bandages from a nearby surgical clinic provided pus from which intact white blood cells could be harvested. When Miescher exposed the cells to various salt solutions, they burst and a slimy porridge emerged that refused further analysis. As white blood cells were known to contain large nuclei, Miescher devised a method to further purify the cells and eventually obtain their nuclei. When he then subjected the nuclei to the same alkaline solutions as before, he noticed a precipitate that differed from previously characterised proteinaceous compounds in several ways. The precipitate was insoluble in the solutions proteins could normally be dissolved in; in contrast to proteins, the substance was rich in phosphorus; and, most notably, it was resistant to protein-digesting enzymes. Miescher concluded that he had discovered a new class of cellular substance, different from proteins, which he named, given its provenance, ‘nuclein’.Of course, Miescher could not have known what he had just discovered and unassumingly entitled the publication of his work, which was repeated by his fastidious supervisor: “On the chemical composition of the pus cells”. The slimy precipitate from the nuclei of burst pus cells turned out later to be the molecule of heredity itself, DNA – something that can nowadays easily be isolated by biology undergraduates using similar chemical procedures as Miescher had used.After a second post-doc studying neural circuits in the spinal cord, Miescher returned to his home town of Basel and published another paper on nuclein in which he showed that it occurs in the spermatozoa of a wide range of animals. This connection between nuclein and the spermatozoa, which were known to be crucial for fertilisation, was the closest Miescher got to asserting the function of DNA. Indeed, he states: “if … a specific substance is the cause of fertilisation, one would without doubt have to think of the nuclein.”View Large Image | View Hi-Res Image | Download PowerPoint SlideBecause of the poor working conditions in Basel, Miescher gave up on the nuclein and studied salmon in the nearby Rhine, as well as reviewing nutrition in Swiss prisons for the government. Unfortunately, Miescher did not live to see the consequences of his discovery. However, as Ralf Dahm, author of several articles on Miescher, states: “Miescher had an instinct for the key questions of his time and his scientific foresight was remarkable. Many of his theories on sexual reproduction and heredity proved to be correct.” (For more on Miescher, see Ralf Dahm's article ‘The molecule from the castle kitchen’, Max Planck Research, 2004, Issue 2, 50–55).Miescher died in 1895, aged only 51. Forty-nine years were to pass before it would be realised that the slimy substance isolated from pus was what carried genetic information.

Apoptosis in Microciona prolifera Allografts

Previous articleNext article No AccessCell BiologyApoptosis in Microciona prolifera AllograftsS. Tepsuporn, J. C. Kaltenbach, W. J. Kuhns, M. M. Burger, and X. Fernàndez-BusquetsS. Tepsuporn1. Mount Holyoke College, South Hadley, MA Search for more articles by this author , J. C. Kaltenbach1. Mount Holyoke College, South Hadley, MA Search for more articles by this author , W. J. Kuhns2. Hospital for Sick Children, Toronto, Canada Search for more articles by this author , M. M. Burger3. Friedrich Miescher Institute, Basel, Switzerland Search for more articles by this author , and X. Fernàndez-Busquets4. University of Barcelona, Barcelona, Spain Search for more articles by this author PDFPDF PLUSFull Text Add to favoritesDownload CitationTrack CitationsPermissionsReprints Share onFacebookTwitterLinkedInRedditEmail SectionsMoreDetailsFiguresReferencesCited by The Biological Bulletin Volume 205, Number 2October 2003 Published in association with the Marine Biological Laboratory Article DOIhttps://doi.org/10.2307/1543251 Views: 25Total views on this site PDF download Crossref reports no articles citing this article.

Negative Regulation of ERK and Elk by Protein Kinase B Modulates c-fos Transcription

In this study, we have identified novel regulatory steps involved in the cross-talk between protein kinase B (PKB) and MAPK signaling pathways. We found that PKB down-regulates the Ras-Raf-MEK-ERK pathway by reducing the activity of ERK, which leads to inactivation of the transcription factor Elk1. In addition, PKB is able to reduce protein levels of Elk1. Both events lead to suppression of serum response element (SRE)-dependent transcription and a consequent decrease in the transcription of SRE-containing genes, such as c-fos. Because activation of the Ras/MAPK cascade is reported to increase c-fos transcription before apoptosis, our results are consistent with a specific role for PKB in promoting cell survival. Decrease in c-Fos protein levels in glioblastoma cells with constitutively active PKB provides further support for our observations. Therefore, our findings delineate a novel mechanism regulating immediate-early transcription, which may be involved in the initial steps in PKB-induced oncogenic transformation.

David Reddy—taking HIV therapy to new frontiers

David Reddy graduated in cellular and molecular biology from the University of Auckland, New Zealand, in 1983. He remained in this area of research for the next 6 years, and in this time completed a Masters followed by a PhD. The focus of his research was on the development of diagnostic assays for detecting HIV, and genetically engineered vaccines for other viral infections. From 1989–1991, he was a molecular neurobiology research fellow at the Friedrich Miescher Institute in Basel, Switzerland. In 1995 he joined F Hoffmann-La Roche in the Pharmaceuticals Divisions' Biotechnology Business group. From 1997–1999 he was the Global Business Unit Head for HIV/AIDS and is currently responsible for the Roche Disease Area Strategy for HIV. He is the leader for the Roche-Trimeris fusion-inhibitor development programme, and dedicates a significant proportion of his time to addressing the challenges of HIV in the developing world.

Reviving Biomedicine: New Basel institute tackles aging and aims to bolster Swiss research (Research funding)

The Alps have protected the Swiss from centuries of invaders, but even the towering mountains can't shield them from aging. Over the next 50 years, the number of people in industrialized nations aged 65 and over is expected to double, and Switzerland is no exception. Although the snowy passes won't keep away old age, a new Swiss institute aims to take on the scientific and societal challenges associated with the demographic change. On 29 November 2001, Gian-Reto Plattner, vice rector of the University of Basel, announced the formation of the Basel Institute for Diseases of Aging (BIDA), which will dedicate itself to investigating the biology of growing old. The institute was conceived in December 2000, when a group of biochemistry and medical researchers from the Novartis Research Foundation's Friedrich Miescher Institute in Basel phoned the vice rector. They wanted to "do something," he says, to focus the considerable science and technology expertise in Basel and the surrounding region, which has been feeling the impact of a spate of negative developments, including last year's closing of the Basel Institute for Immunology and a pronounced exodus of scientists. A brainstorming session led to the idea of a center of excellence in biomedical research. The group hoped to combine the region's strengths--a university, teaching hospitals, and biotechnology and pharmaceutical companies--to address a topic that is "scientifically novel and interesting and [that] at the same time somehow touches society's interest in a strong way," says Plattner. Aging topped the list of potential areas of study, and BIDA was born. BIDA will operate as an independent, nonprofit research institution associated with the University of Basel. In addition, BIDA will partner with the rest of the biomedical research community in the area to develop a comprehensive science and technology network that will strengthen research and promote economic growth. This group will coordinate resources such as tissue banks, bioinformatics services, facilities for studying animals that model human diseases, and molecular and cellular imaging systems--and negotiate arrangements for their shared use. Rather than study geriatric diseases per se, BIDA will focus on the conditions that predispose people to these disorders, many of which begin well before old age takes hold. The institute's research will home in on degenerative processes, for example, such as cancer metastasis and the neurodegeneration of Alzheimer's disease. The full-grown BIDA will comprise about 20 to 25 research groups totaling roughly 300 researchers. Local government, the University of Basel, and the Novartis Research Foundation provided seed money for a feasibility study and a planning phase. The institute itself will require an additional initial investment of approximately 100 million Swiss francs (US$61.2 million) for building and equipment, plus yearly operating costs of about 40 million Swiss francs (US$24.5 million). The target date for completion of the institute is roughly 2008. But if all goes well, the institute will begin to operate in 2003 on rented premises, says Plattner. BIDA has assembled a star-studded council to hit up public and private sources for the money still required to launch the project. The council includes Nobel laureates, the former head of the Union Bank of Switzerland, and other leaders from government, science, and industry. "We will try to be a little bit American in the way it's done," says Plattner, referring to optimism, enthusiasm, and willingness to go after private money. "Whether that works with Swiss people, we have to find out." --Giselle Weiss Further Reading • Swiss National Science Foundation http://www.snf.ch/default_en.asp • Friedrich Miescher Institute http://www.fmi.ch • Biozentrum at the University of Basel http://www.biozentrum.unibas.ch

Life sentences: Detective Rummage investigates.

Life sentences: Detective Rummage investigates.

A TORrific ATP sensor

Apositive regulator of growth called mTOR (mammalian Target of Rapamycin) is a direct detector of ATP levels, according to George Thomas (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) and colleagues. This connection from ATP to growth may explain why certain oxygen- and ATP-starved tumor cells are particularly sensitive to the mTOR- inhibitor rapamycin, as such tumors, through increased glycolysis and ATP production, may use the mTOR signaling pathway to proliferate.Dennis et al. began their studies with mTOR kinase assays. Results in several labs had been spotty, to the extent that mTOR's qualifications as a kinase were in question. “We were about ready to toss it out,” says Thomas. Figure All roads lead to TOR. But, by chance, the authors discovered that higher ATP concentrations converted mTOR into a robust kinase. Dropping ATP levels in vitro, or adding glycolytic inhibitors in vivo resulted in a drop in mTOR-specific phosphorylations of target proteins. Apparently mTOR can act as a cellular ATP sensor because it has a weak, millimolar affinity for ATP. When both ATP and amino acids are available, mTOR upregulates translation and ribosome biogenesis, and downregulates autophagy. The remaining question is whether cancer cells that have gained a selective growth advantage by boosting mTOR activity do so through raising intracellular ATP levels. ▪ Reference: Dennis, P.B., et al. 2001. Science. 294:1102–1105. [PubMed]

Tumor suppression by a proapoptotic calcium-activated chloride channel in mammary epithelium.

Little is known of the roles played by ion channels in cancer. Here we describe a pair of closely related calcium-activated chloride channels whose differential regulation in normal, apoptotic, and transformed mouse cells suggests that channel function is proapoptotic and antineoplastic. While mCLCA1 predominates over mCLCA2 under normal physiological conditions, this relationship is reversed by apoptotic stress both in developing mammary gland and in cultured HC11 mammary epithelial cells. Consistent with an apoptosis-promoting role, splicing of mCLCA2 is disrupted in apoptosis-resistant tumor cell lines and in HC11 cells selected for resistance to detachment-induced apoptosis (anoikis). Unexpectedly, mCLCA1 message is also down-regulated in these cells by at least 30-fold. These results suggest that both genes antagonize survival of mammary tumor cells by sensitizing them to anoikis. When MCF7 or HEK293 tumor cells were transfected with plasmids encoding either mCLCA1 or mCLCA2, colony formation was greatly reduced relative to a vector-transfected control, demonstrating that calcium-sensitive chloride channel (CLCA) expression is deleterious to tumor cell survival. Furthermore, mammary epithelial cells overexpressing mCLCA2 had twice the rate of apoptosis of normal cells when subjected to serum starvation and formed multinuclear giants at a high frequency in normal culture, suggesting that mCLCA2 can promote either apoptosis or senescence.

Friedrich Miescher Prize awardee lecture review. A conserved family of nuclear export receptors mediates the exit of messenger RNA to the cytoplasm.

The distinguishing feature of eukaryotic cells is the segregation of RNA biogenesis and DNA replication in the nucleus, separate from the cytoplasmic machinery for protein synthesis. As a consequence, messenger RNAs (mRNAs) and all cytoplasmic RNAs from nuclear origin need to be transported from their site of synthesis in the nucleus to their final cytoplasmic destination. Nuclear export occurs through nuclear pore complexes (NPCs) and is mediated by saturable transport receptors, which shuttle between the nucleus and cytoplasm. The past years have seen great progress in the characterization of the mRNA export pathway and the identification of proteins involved in this process. A novel family of nuclear export receptors (the NXF family), distinct from the well-characterized family of importin beta-like proteins, has been implicated in the export of mRNA to the cytoplasm.

A random walk from the cello to the lab

A random walk from the cello to the lab

DNA pioneers and their legacy

In this entertaining account of the origins of modern molecular biology, the lives of pioneering scientists in the field of nucleic acid research, and the discovery of DNA, Ulf Lagerkvist speaks not only to scientists but to all students and general readers with an interest in science. The author, whose career in the nucleic acid field began in the late 1940s, recreates historical episodes from the nineteenth and early twentieth centuries and introduces for a modern audience the scientists whose discoveries revolutionized the field of biology. Knowledge of these pioneers as professionals and as human beings, Lagerkvist believes, may help us see modern problems in a new light and appreciate the greatness of the researchers who contributed to the foundations of molecular biology and biochemistry. Among these scientific pioneers was nineteenth-century biochemist Friedrich Miescher, discoverer of nuclein, the material now known as DNA. The book also explores early research into general problems of the chemistry of biological materials. Lagerkvist vividly describes the research of such influential scientists as Albrecht Kossel, another early leading figure; Emil Fischer, who received the Nobel Prize in 1902 for his work on carbohydrates and purines and was regarded as the foremost chemist of his time; P. A. Levene, known for his discoveries concerning the structure of nucleotides and the way these nucleic acid building blocks are linked to one another; and Oswald T. Avery, often considered the grandfather of molecular genetics.

Liver or lung colonization by F9 teratocarcinoma cells follows specific interactions with the target organ : Dario Rusciano, Patrizia Lorenzoni and Max M. Burger. Friedrich Miescher Institute, P.O. Box 2543, CH-4002 Basel, Switzerland

Liver or lung colonization by F9 teratocarcinoma cells follows specific interactions with the target organ : Dario Rusciano, Patrizia Lorenzoni and Max M. Burger. Friedrich Miescher Institute, P.O. Box 2543, CH-4002 Basel, Switzerland

The c-erbB-2 protein as a target for directing cytotoxic agents to tumor cells : N.E. Hynes, I.-M. Harwerth, W. Wels; Friedrich Miescher Institute P.O. Box 2543, 4002 Basel, Switzerland

The c-erbB-2 protein as a target for directing cytotoxic agents to tumor cells : N.E. Hynes, I.-M. Harwerth, W. Wels; Friedrich Miescher Institute P.O. Box 2543, 4002 Basel, Switzerland

Tenascin is involved in extracellular matrix mediated tissue interactions during development and oncogenesis : R. Chiquet-Ehrismann, E.J. Mackie, C.A. Pearson and T. Sakakura. Friedrich Miescher Institut, CH-4002 Basel

Tenascin is involved in extracellular matrix mediated tissue interactions during development and oncogenesis : R. Chiquet-Ehrismann, E.J. Mackie, C.A. Pearson and T. Sakakura. Friedrich Miescher Institut, CH-4002 Basel

Changes in the distribution of tenascin during tooth development: [formula omitted], Institute of Dentistry, Univ. of Helsinki, SF-00280 Helsinki, Finland and Friedrich Miescher Institute, CH-4002, Basel, Switzerland

Changes in the distribution of tenascin during tooth development: [formula omitted], Institute of Dentistry, Univ. of Helsinki, SF-00280 Helsinki, Finland and Friedrich Miescher Institute, CH-4002, Basel, Switzerland

The growth regulation of cancer metastases by their host organ: [formula omitted] Department of Biochemistry, Biocentre and Friedrich Miescher Institute, Basel, Switzerland

The growth regulation of cancer metastases by their host organ: [formula omitted] Department of Biochemistry, Biocentre and Friedrich Miescher Institute, Basel, Switzerland

Genetic analysis of the antero-posterior pattern in the embryo of [formula omitted]: Christiane Nüsslein-Volhard, Friedrich Miescher Laboratorium der Max Planck Gesellschaft, Tübingen, FRG

Genetic analysis of the antero-posterior pattern in the embryo of [formula omitted]: Christiane Nüsslein-Volhard, Friedrich Miescher Laboratorium der Max Planck Gesellschaft, Tübingen, FRG

Mitosis and metabolic organization

This review is addressed to the problem of interpreting the nature of metabolic events associated with mitosis. Such events may initiate, support, or be a consequence of the process; but they all share the property of reflecting a physical reorganization of the cell more extreme and more extensive than most events in its history. It is, then, the relationship between structural and metabolic changes that constitutes the substance of this communication. Cytology and metabolism have had a long history of separation; their association is less than 30 years old. Fleming's resolution of mitosis as a longitudinal splitting and separation of chromosomesa milestone in the history of cell biology-was published in 1882 (6). Ten years later Eduard Buchner marked the start of modern metabolic studies by demonstrating fermentation in yeast extracts. But for nearly 40 years after Buchner made his fruitful discovery, physical chemistry and not catalysis was at the heart of cellular research. In 1922, Wilson, cutting the broadest of swaths in his survey of the cell, concluded that "life as we know it is indeed -inseparably bound up with matter in the colloidal state. This conception seems likely to prove as fruitful in cytology as it has been in physiology" (114). In no less positive a way did the historian of biology, Nordenskiold, sum up the scene at that time: "That branch of chemical research which has had its greatest success in our own day and has excited the keenest interest is undoubtedly physical chemistry; each stage of its progress has at once been applicable to the living substance" (73). Such was the dominant view of cell biologists ten years after Warburg (105) had demonstrated that the oxidative capacity of liver cells could be separated in the form of sedimentable particles. To trace the beginnings of cytochemistry, young though it is, one must leap well across the many years during which cell physiology found its most forward expression in terms of colloidal chemistry. In 1871, ten years before mitosis had been resolved, Friedrich Miescher