Category Archives: Biochemistry

R-loops break walls of gene silencing

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From :http://www.news.ucdavis.edu/search/news_detail.lasso?id=10165

Researchers at the University of California, Davis, have figured out how the human body keeps essential genes switched “on” and silences the vast stretches of genetic repeats and “junk” DNA.

Frédéric Chédin, associate professor in the Department of Molecular and Cellular Biology, describes the research in a paper published today (March 1) in the journal Molecular Cell. The work could lead to treatments for lupus and other autoimmune diseases, by reversing the gene-silencing process known as cytosine methylation.

“R-loops” are the key, say graduate student Paul Ginno, Chédin and colleagues. The loops emerge in the RNA transcription process in DNA sections that are rich in cytosine and guanine, the C and G in the four-letter DNA code. These C and G stretches serve as “on” switches, or promoters, for about 60 percent of human genes.

Scientists have known since the 1980s that these so-called CG island promoters are not subject to methylation. But, Chédin said, the mechanism has been a long-standing mystery.

The UC Davis researchers built a catalog of almost 8,000 CG islands in the human genome, studied their DNA sequences and found the CG sequences to be skewed toward having one strand of the double helix rich in guanine, and the complementary strand rich in cytosine.

Then, in RNA transcription, the G-rich RNA remains stably bound to a C-rich DNA strand, forcing the G-rich DNA strand into a loop — which then prevents methylation.

DNA methylation is considered part of the new field of epigenetics, which studies inheritable genetic changes that are not directly coded in the DNA sequence. However, the new work shows that, at least at CG islands, the epigenetic state is determined by the DNA sequence.

Scientists know that reduced methylation of DNA plays a key role in triggering autoimmunity in lupus, Chédin said. However, the molecular events behind this DNA under-methylation have been unclear.

“Our work establishes that excessive R-loop formation may drive under-methylation and autoimmunity,” Chédin said.

Co-authors: Paul Lott, graduate student; Holly Christensen, undergraduate; and Ian Korf, associate professor in the Department of Molecular and Cellular Biology and the Genome Center.

The National Institutes of Health and the Foundation for Prader-Willi Research supported the project.

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Colorado researcher discovers mechanism for changing adult cells into stem-like cells

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A scheme of the generation of induced pluripot...

A scheme of the generation of induced pluripotent stem (iPS) cells. 1. Isolate and culture host cells. e.g. mouse embryonic fibroblasts and adult human dermal fibroblasts. 2. Introduce the ES specific genes (iPS factors) into the cells by using retrovirus vector. Red cells indicate the cells expressing the exogenous genes. 3. Harvest and culture the cells according to the method for ES cell culture using feeder cells (gray). 4. A subset of the cells generates ES-like colonies, that is, iPS cells;Image via Wikipedia

 

In 2006, Dr. Shimya Yaminaka of Kyoto University in Japan set the stem cell and regenerative medicine research world on fire when he successfully transformed differentiated mouse skin cells into cells that looked and behave like embryonic stem cells. Embryonic stem cells, the subject of much controversy when used in research, have the ability to differentiate into any type of tissue.

Yaminaka’s creation of induced pluripotent stem cells [iPSCs] meant that in the future, research to improve human disease might be able to use iPSCs in lieu of embryonic stem cells. Since then, researchers around the world have been able to replicate his process. However, no one has been able to unlock the mechanism that allows cells to be regressed from differentiated to undifferentiated cells—until now.

University of Colorado Cancer Center researcher Chuan-Yuan Li, PhD, and his group have discovered that so-called “grim-reaper” caspase genes are the gatekeepers that can open the door to allow differentiated adult cells to regress to undifferentiated iPSCs.

Caspases, or cysteine-aspartic proteases/cysteine-dependent aspartate-directed proteases are part of a group of enzymes known as cysteine proteases. Caspases play essential roles in apoptosis (programmed cell death-can occur in a sinle cell surrounded by viable cells), necrosis (premature cell death caused by factors outside a tissue such as trauma or infection-occurs in many cells simultaneously), and inflammation.They exist within the cell as inactive pro-forms or zymogens. These zymogens can be cleaved to form active enzymes following the induction of apoptosis. Failure of apoptosis is one of the main known contributiors to tumour development and autoimmune diseases; this, coupled with the unwanted apoptosis that occurs with ischemia or Alzheimer’s disease, has stimulated interest in caspases as potential therapeutic targets since they were discovered in the mid-1990s.[1,2]

“By doing experiments in which we added caspase inhibitor genes to the Yaminaka protocol, we discovered that when caspases are turned off, you cannot make IPSCs,” says Li, professor of radiation oncology at the University of Colorado School of Medicine. “We were able to shut down the process almost completely.”

The discovery is the cover article in the Oct. 8, 2010 issue of Cell Stem Cell.

“For practical reasons, the discovery is important because even though the transformation to iPSCs is a straightforward process on surface, it is not very efficient, and this information can help increase efficiency,” Li says. “It can also help with the problem of cells that don’t complete the transformation process acting like cancer cells. And from a purely scientific perspective, it is fascinating to understand why the magic happens.”

Li’s group had been working on the roles of caspases in wound healing when Yaminaka published his initial iPSC work in mice. That got Li thinking about potential roles of caspases in iPSC generation.

“I thought maybe caspases could also induce iPS cells instead of the four transcriptional factors that Yamanaka used,” he says. “If that was true, it would be very exciting.”

For six months, his group tried different experiments using various caspase genes to coax human skin cells into iPS cells, but they had no success. Although caspases were not sufficient to make iPS cells, Li kept going with the idea that caspases were somehow involved.

They made their discovery when they introduced the caspase inhibitors into skin cells, which almost completely shut down the induction of iPS cells.

Caspases, Li says, appear to loosen up the built-in controls that make a cell differentiated or undifferentiated, just like a clutch allows a driver to switch gears while driving. Undifferentiated stem-like cells and differentiated cells from one person have the exact same genes. The difference between them is which genes are turned on or off.

In other words, he says, caspases could be the key to a kind of cellular reincarnation—taking a cell that, during human development, became a skin cell back to its original state to become any kind of cell.

“About twenty years ago, a scientist who was among the first to clone the caspase 3 gene named the gene Yama, the Hindu Lord of Death who was responsible for both killing a being and setting him on his way into his reincarnated life,” Li said. “It is now becoming clear that caspases don’t just kill, but they can change the cell’s fate. They could be a mediator of epigenetic changes in multi-cellular organisms.”

###

Members of Li’s research group who were integral to the studies include Fang Li, the paper’s lead author, Zhimin He, Jingping Shen, Qian Huang, Wenrong Li, Xinjian Liu, Yujun He and Frank Wolf.

Sources:

  1. http://www.eurekalert.org/pub_releases/2010-10/uocd-uoc100610.php
  2. Fang Li, Zhimin He, Jingping Shen, Qian Huang, Wenrong Li, Xinjian Liu, Yujun He, Frank Wolf, Chuan-Yuan Li. Apoptotic Caspases Regulate Induction of iPSCs from Human Fibroblasts. Cell Stem Cell, Volume 7, Issue 4, 508-520, 8 October 2010 DOI: 10.1016/j.stem.2010.09.003

References

  1. http://www.sgul.ac.uk/depts/immunology/~dash/apoptosis/caspases.html
  2. http://www.bioscience.org/news/scientis/caspase.htm
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Exmaining processes at the surface of growing crystals

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Single Protein crystal of Lysozyme

Single Protein crystal of Lysozyme;Image via Wikipedia

Washington, D.C. (September 14, 2010) — Because one of the main bottlenecks in determining the structure of protein molecules is producing good isolated single crystals, improved crystallization techniques would be useful in a wide range of genomics and pharmaceutical research.

Research reported in The Journal of Chemical Physics uses fluorescence correlation spectroscopy (FCS) to investigate the processes at the surface of a growing crystal. By focusing a laser on the crystal surface and measuring the resulting fluorescence, FCS can resolve dimensions as small as a single wavelength of the light.

FCS

Fluorescence correlation spectroscopy (FCS) is one of the many different modes of high-resolution spatial and temporal (relating to time) analysis of extremely low concentrated biomolecules.”In contrast to other fluorescence techniques, the parameter of primary interest is not the emission intensity itself, but rather spontaneous intensity fluctuations caused by the minute deviations of the small system from thermal equilibrium. In general, all physical parameters that give rise to fluctuations in the fluorescence signal are accessible by FCS. It is, for example, rather straightforward to determine local concentrations, mobility coefficients or characteristic rate constants of inter- or intramolecular reactions of fluorescently labeled biomolecules in nanomolar concentrations. FCS is a is a versatile technique that already has demonstrated its vast possibilities for many different problems.It is often used together with other confocal fluorescence readout techniques – one of the standard tools used for high-throughput screening, combining very short data acquisition times with straightforward analysis.[1]

“Another advantage of fluorescence is that it provides a high signal-to-noise ratio,” says author Shinpei Tanaka of Hiroshima University in Japan. “We are able to measure very dilute solutions at the crystal interface.”

Research Findings

The researchers found that when single tetragonal crystals of egg-white lysozyme formed, there was no concentration gradient between the solution and the crystal surface. However, in formation of clumps of needle-like branched crystals, called spherulites, the observed concentration at the surface was several times higher than that of the bulk solution. The authors attributed the difference to aggregates of loosely bound molecules near the interface.

Characterization of the dynamics near the crystal by FCS may provide direction for improving the crystallization process — currently as much an art as a science, based on trial and error — because the spherulites are not usable for structural characterizations.

“Although we knew something was different between the two crystal forms, the degree of concentration of the molecules in spherulites compared to that of the homogeneous state around tetragonal single crystals was surprising,” says Tanaka.

The analytical result could lead to improvements in isolation of good crystals of biomolecules. For example, the results suggest that local heating by a laser could be used to control local concentrations and avoid spherulite formation.

Sources

“Slow molecular dynamics close to crystal surfaces during crystallization of a protein lysozyme studied by fluorescence correlation spectroscopy” by Shinpei Tanaka appears in The Journal of Chemical Physics. http://link.aip.org/link/jcpsa6/v133/i9/p095103/s1

http://www.eurekalert.org/pub_releases/2010-09/aiop-hdy091310.php

References

[1] http://www.biophysics.org/Portals/1/PDFs/Education/schwille.pdf

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Watercress may ‘turn off’ breast cancer signal

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Watercress Beds - Headbourne Worthy

Watercress Beds - Headbourne Worthy;Image by neilalderney123 via Flickr

New scientific research from the University of Southampton has revealed that a plant compound in watercress may have the ability to suppress breast cancer cell development by ‘turning off’ a signal in the body and thereby starving the growing tumour of essential blood and oxygen.

The research, unveiled at a press conference today (14 September 2010), shows that the watercress compound is able to interfere with the function of a protein which plays a critical role in cancer development.

As tumours develop they rapidly outgrow their existing blood supply so they send out signals which make surrounding normal tissues grow new blood vessels,a process called angiogenesis, into the tumour which feed them oxygen and nutrients. Angiogenesis is the physiological process involving the growth of new blood vessels from pre-existing vessels.It is a normal and vital process in growth and development, as well as in wound healing. However, it is also a fundamental step in the transition of tumors from a dormant state to a malignant one.

The research, led by Professor Graham Packham of the University of Southampton, shows that the plant compound (called phenylethyl isothiocyanate) found in watercress can block this process, by interfering with and ‘turning off’  the function of a protein called Hypoxia Inducible Factor (HIF).HIF is a transcription factor that responds to decreases in  oxygen levels or hypoxia,in the cellular environment.”

“Dietary intake of isothiocyanates (ITC) has been associated with reduced cancer risk. The dietary phenethyl ITC (PEITC) has previously been shown to decrease the phosphorylation of the translation regulator 4E binding protein 1 (4E-BP1). Decreased 4E-BP1 phosphorylation has been linked to the inhibition of cancer cell survival and decreased activity of the transcription factor hypoxia-inducible factor (HIF), a key positive regulator of angiogenesis, and may therefore contribute to potential anti-cancer effects of PEITC.”[1] The current study examined the the in vitro and in vivo effects of watercress, which is a rich source of PEITC.

Professor Packham, a molecular oncologist at the University of Southampton, comments: “The research takes an important step towards understanding the potential health benefits of this crop since it shows that eating watercress may interfere with a pathway that has already been tightly linked to cancer development.”

“Knowing the risk factors for cancer is a key goal and studies on diet are an important part of this. However, relatively little work is being performed in the UK on the links between the foods we eat and cancer development.”

Working with Barbara Parry, Senior Research Dietician at the Winchester and Andover Breast Unit, Professor Packham performed a pilot study in which a small group of healthy participants who had previously been treated for breast cancer, underwent a period of fasting before eating 80g of watercress (a cereal bowl full) and then providing a series of blood samples over the next 24 hours.

The research team was able to detect significant levels of the plant compound PEITC in the blood of the participants following the watercress meal, and most importantly, could show that the function of the protein HIF was also measurably affected in the blood cells of the women.

The researchers stated that “dietary intake of watercress may be sufficient to modulate this potential anti-cancer pathway”.However “further investigations with larger numbers of participants are required to confirm these findings”.[1]

The two studies, which have been published in the British Journal of Nutrition and Biochemical Pharmacology, provide new insight into the potential anti-cancer effects of watercress, although more work still needs to be done to determine the direct impact watercress has on decreasing cancer risk.[1,2,3]The findings build on studies that have shown people who vegetables rich in isothiocyanates, such as broccoli and cabbage, are at lower risk of developing cancer [4]

Watercress Alliance member Dr Steve Rothwell says: “We are very excited by the outcome of Professor Packham’s work, which builds on the body of research which supports the idea that watercress may have an important role to play in limiting cancer development.”

A summary of the research has been accepted for inclusion in the Breast Cancer Research Conference which is taking place in Nottingham from 15 to 17 September.

Sources:

[1] Syed Alwi SS, Cavell BE, Telang U, Morris ME, Parry BM, Packham G.(2010)In vivo modulation of 4E binding protein 1 (4E-BP1) phosphorylation by watercress: a pilot study.Br J Nutr. 2010 Jun 15:1-9. [Epub ahead of print]

[2]Inhibition of hypoxia inducible factor by phenethyl isothiocyanate (2009)Biochemical Pharmacology
Volume 78, Issue 3, 1 August 2009, Pages 261-272

[3] Press release:http://www.soton.ac.uk/mediacentre/news/2010/sep/10_94.shtml

[4]Compounds in broccoli, cauliflower, and watercress block lung cancer progression

Further Reading:

Five reasons you should eat watercress

Dietary Chemopreventive Phytochemicals: Too Little or Too Much?

Watercress wiki

Watercress Recipes

http://www.watercress.co.uk/recipes/

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Flower Could Revolutionise Leukemia Treatment

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From the Daily Mail

Baby's Breath

“Scientists unveiled a major medical breakthrough that could revolutionise the treatment of leukaemia patients and save thousands of lives.

Experts have discovered that an extract from the white flower commonly known as Baby’s Breath can boost the efficiency of anti-cancer drugs by a staggering million times.

They found that molecules called saponins, extracted from the Gypsophila Paniculata plant, appear to break down the membrane of cancer cells.”



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Alzheimers memory problems are caused by amyloid beta oligomers,not amyloid plagues

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AD-3

This is a single Alzheimer's disease plaque - the green shows fibrils and the red shows other assembly states of beta-amyloid;Image by Zerd via Flickr

Using a new mouse model of Alzheimer’s disease, researchers at Mount Sinai School of Medicine have found that Alzheimer’s pathology originates in Amyloid-Beta (Abeta) oligomers in the brain, rather than the amyloid plaques previously thought by many researchers to cause the disease.[2]

Alzheimer disease (AD) is the leading cause of dementia, affecting more than 26 million people worldwide.Clinically, the disease is characterized by progressive memory loss and a decline in cognitive abilities.[1]

Several symptomatic treatments are in use for AD; however, no disease-modifying therapies are currently available.[1]

The search for an Alzheimer drug is hindered by lack of understanding of the disease and also by the lack of suitable tests to measure efficacy of trial drugs.Currently the only way to measure efficacy in Alzheimer drug clinical trials is to use psychological tests which measure how well a patient is doing to how they were a year ago.There is quite a lot of variability in Alzheimer’s patients as to how they are doing mentally and there can be large variations in results.[3] Thus,in order to  to account for these variations the trials need to be conducted over many years.Imaging and immunoassays such as the ELISA assay are also used to see if the drug is working as expected.However these techniques alone are not enough as they measure physical processes such as antibody drugs binding to the target plagues which indicates if the drug is doing its intended while the mental tests discussed above tend to be quite variable in their own right which makes attributing changes in cognitive function to the drug challenging.

The study, which was supported by the  “Oligomer Research Consortium” of the Cure Alzheimer Fund and a MERIT Award from the Veterans Administration, appears in the journal Annals of Neurology.

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits.Abnormal accumulation of amyloid in organs may lead to amyloidosis,something any fans of the TV show ‘House’ will be all too familiar with,and may play a role in various other neurodegenerative diseases such as Alzheimer’s.

Amyloid beta(Aβ or Abeta) is a peptide of 39–43 amino acids which appears to be the main constituent of amyloid plaques in the brains of Alzheimer’s disease patients and which also forms aggregates coating cerebral blood vessels in cerebral amyloid angiopathy. These plaques are composed of a tangle of regularly ordered fibrillar aggregates called amyloid fibers,[1] a protein fold that is shared by other peptides such as the prions associated with protein misfolding diseases.

“The buildup of amyloid plaques was described over 100 years ago and has received the bulk of the attention in Alzheimer’s pathology,” said lead author Sam Gandy, MD, PhD, Professor of Neurology and Psychiatry, and Associate Director of the Alzheimer’s Disease Research Center, Mount Sinai School of Medicine. “But there has been a longstanding debate over whether plaques are toxic, protective, or inert.” [2,4]

Several research groups had previously proposed that rather than plaques, floating clumps of amyloid (called oligomers) are the key components that impede brain cell function in Alzheimer’s patients. To study this, the Mount Sinai team developed a mouse that forms only these oligomers, and never any plaques, throughout their lives.

In this case,oligomers refer to protein complexes composed of two or more subunits.Protein complexes are a form of quaternary structure with proteins in the complex being  linked by non-covalent protein-protein interactions.Different protein complexes have different degrees of stability over time and  complex formation often serves to activate or inhibit one or more of the complex members. In this way protein complex formation can be similar to phosphorylation. A method that is commonly used for identifying the members of protein complexes is immunoprecipitation.

The researchers found that the mice that never develop plaques were just as impaired by the disease as mice with both plaques and oligomers. Moreover, when a gene that converted oligomers into plaques was added to the mice, the mice were no more impaired than they had been before.

“These findings may enable the development of neuroimaging agents and drugs that visualize or detoxify oligomers,” said Dr. Gandy. “New neuroimaging agents that could monitor changes in Abeta oligomer presence would be a major advance. Innovative neuroimaging agents that will allow visualization of brain oligomer accumulation, in tandem with careful clinical observations, could lead to breakthroughs in managing, slowing, stopping or even preventing Alzheimer’s.[2]

“This is especially important in light of research reported in March showing that 70 weeks of infusion of the Abeta immunotherapeutic Bapineuzumab® ,a much anticipated humanized monoclonal antibody developed by Elan to bind to the plaques, cleared away 25 percent of the Abeta plaque, yet no clinical benefit was evident.” [2]

###

The Mount Sinai team included Michelle Ehrlich, MD, Professor of Pediatrics, Neurology, and Genetics and Genomic Sciences, and John Steele, a Mount Sinai graduate student, who performed the key analyses of the behavioral data. Dr. Charles Glabe, an oligomer expert and a member of the Cure Alzheimer Fund research consortium, is also a co-author of the paper. Dr Gandy is also a neurologist at the James J Peters Veterans Affairs Medical Center, an affiliate of Mount Sinai School of Medicine.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of few medical schools embedded in a hospital in the United States. It has more than 3,400 faculty in 32 departments and 15 institutes, and ranks among the top 20 medical schools both in National Institute of Health funding and by U.S. News & World Report. The school received the 2009 Spencer Foreman Award for Outstanding Community Service from the Association of American Medical

Colleges.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2009, U.S. News & World Report ranked The Mount Sinai Hospital among the nation’s top 20 hospitals based on reputation, patient safety, and other

patient-care factors. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and about 530,000 outpatient visits took place.

References

1.  http://www.medscape.com/viewarticle/717219

2.http://www.eurekalert.org/pub_releases/2010-04/tmsh-amp042710.php

3.http://health.nytimes.com/ref/health/healthguide/esn-alzheimers-qa.html

4.http://www.sciencedaily.com/releases/2009/11/091123114813.htm

Further Reading

Active and passive Immunotherapy for Neurodegenerative Disorders (pdf)

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A15416&rendertype=figure&id=A15420

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US Judge Rules That Gene Patents Are Invaild

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BRCA1-Gene located on chromosome 17.

BRAC1 Gene on Chromosome 17,Image via Wikipedia

In a powerful ruling a district Judge  for the Southern District of New York in the  US has ruled that patents on genes are invalid.Approximately 20 per cent of the human genome is currently subject to a patent.The judge,Robert Sweet,has overturned the patents on two genes linked to breast and ovarian cancer on the grounds that they’re not man-made, but products of nature. A company Myriad Genetics had previously patented the BRCA1 and 2 genes which were the subject of the ruling.They were charging women more than $3000 for one test for genetic mutations and banned them from getting a second opinion.

BRAC1 and BRAC2

BRAC 1 and 2 are human tumor suppressor genes that produce proteins which combine with other tumor suppressors to repair damaged DNA and destroy the cell if the DNA is unrepairable. Some inherited mutations in these genes lead to uncontrolled cell division i.e. cancer and testing for these mutations can determine the risk of contracting ovarian or breast cancer.

Court Case

The case was taken to court by the American Civil Liberties Union (ANLU) and individual breast cancer patients who argued that the patent stifled medical research.This ruling  follows much earlier rulings in Europe by the European Patent Office in 2004 which revoked Myraid genetics European patents on the BRAC1 and 2 genes ,effectively locking them out of the European market.However those patents were revoked because the charity Cancer Research UK had filed its patent on the BRAC2 gene first and the patent on the BRAC1 was deemed not ‘inventive’.

Previous Fate of Myriad Genetics Patents in Europe

The European Patent Organisation (EPO) had originally granted 3 patents on the BRCA1 gene (EP-B-699754, EP-B-705903, EP-B-705902) to Myriad Genetics. The patents, and the option by the patent holder to strictly exert its monopoly right by requesting that all diagnostic testing be done at its laboratory in the United States,evoked strong reactions throughout Europe. Several opposition procedures had been started against these patents. After oral hearings at the EPO in Munich in May 2004, the first patent was revoked due to discrepancies of about 10 DNA letters between the BRCA1 gene sequence described in Myriad’s patent, issued in 2001, and the sequence in Myriad’s original patent application on the gene in 1994.By the time that Myriad had resubmitted the correct sequence it was found that the sequence had already been openly published elsewhere-this is known as ‘prior art‘.This deemed it automatically unpatentable as inventions have to be original/ inventive to be patented.At oral proceedings in January 2005, the other two patents were also severely limited in scope.

Current Law on Gene Patents

Patents cannot be granted on things found in nature and logically you would think that genes would fall into the

nature category since they are not man-made.However, patents can be granted on gene sequences as long as these sequences are claimed in the form of ‘isolated DNA’,that is DNA which has been purified from the body.This practice is based on the view that DNA should not be treated any differently to another chemical compound and that its isolation from the body renders it patentable as it has been transformed into a different character.Supporters of gene patents look at this as getting a patent on identifying the gene and not on the actual gene.However many scientists in the genomics and molecular biology field consider this to be a ‘lawyers trick’ as it gets around the problem of patenting DNA in the body which cannot be done since it constitutes a component of ‘nature’,but which in practical terms produces the same results as if we had patented DNA in the body

Breast cancer associated protein, BRCA1.

US Court ruling

DNA is essentially the physical form of biological information,and is distinct in its essential characteristics from other chemicals found in nature. It is concluded that DNA’s existence in an “isolated” form alters neither this fundamental quality of DNA as it exists in the body i.e. in nature  nor the information it encodes. Therefore, the patents at issue which were on  “isolated DNA” containing sequences found in nature are unsustainable as a matter of law and are deemed unpatentable subject matter under 35 USC 101.

Also because the claimed comparisons of DNA sequences are abstract mental processes ,they also constitute unpatentable subject matter under Section 101

Comments

Myriad Genetics is likely to appeal this ruling so the story is far from over but its a nice step forward for research in this area.

References

Europe revokes controversial gene patent-New Scientist 2004

The European opposition against the BRCA gene patents.-Paper from Fam Cancer. 2006;5(1):95-102.

US Judge rules cancer gene patent invalid-abc.net.au

Court:Essentially All Gene Patents Are Invalid-patentlyO (patent law blog)

Human Genetics Commission

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Irish Researchers Uncover New Data on Arl13b function in Joubert Syndrome

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A cilium (plural cilia) is an organelle found ...

A cilium (plural cilia) is an organelle found in eukaryotic cells.Image via WikipediaIntroduction

Introduction

Researchers in Ireland have gained a new understanding of the role played by the cilial protein Arl13b in Joubert syndrome (JS). The findings will be published online March 15 in the Journal of Cell Biology.Joubert Syndrome is a rare brain malformation characterized by the absence or underdevelopment of the cerebellar vermis – an area of the brain that controls balance and coordination.[1]

Arl3b

The name ‘Arl13b’ stands for ‘ADP-ribosylation factor-like 13B’ and is also known as ‘ADP-ribosylation factor-like protein 2-like 1′ and ‘ARL2-like protein 1′ or ‘ARL2L1′.It is a member of the Arf/Arl (Arf-like) family of small GTPases.GTPases are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP).The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases. [2]

Study of Arl13b

The most common features of Joubert syndrome in infants include  decreased muscle tone (hypotonia),abnormally rapid breathing (hyperpnea), jerky eye movements (oculomotor apraxia), mental retardation, and the inability to coordinate voluntary muscle movements (ataxia). Physical deformities  such as extra fingers and toes (polydactyly), cleft lip or palate, and tongue abnormalities may also be present. Kidney and liver abnormalities can develop, and seizures can also occur.

Most cases of Joubert syndrome are sporadic (not inherited). In some families, however, Joubert syndrome appears to be inherited in an autosomal recessive manner (meaning both parents  have a copy of the mutation) via mutation in a number of genes, including NPHP1, AHI1, and CEP290.

Prognosis with JS

The prognosis for children depends on whether the cerebellar vermis is entirely absent or just underdeveloped.Some children may only exhibit a mild form of the disorder with good mental ability and minimal motor problems while others may suffer severe motor disablility and moderate mental retardation.The syndrome was first identified by pioneering pediatric neurologist Marie Joubert in Montreal, Canada, while working at the Montreal Neurological Institute and McGill University[1,3]

Neuroradiological Hallmarks of JS

The neuroradiological hallmark in JS is a peculiar malformation of the midbrain-hindbrain junction known as the “molar tooth sign” (MTS), consisting of cerebellar vermis hypoplasia (cerebellar vermis underdevelopment ) or dysplasia (developmental abnormality), thick and horizontally oriented superior cerebellar peduncles, and an abnormally deep interpeduncular fossa (somewhat lozenge-shaped area of the base of the brain).[4]

References

2. Kenji Kontani, Yuji Hori, Toshiaki Katada (2009)Arf-like protein 13B,UCSD-Nature Molecule Pages,doi:10.1038/mp.a003975.01

3.Joubert M, Eisenring JJ, Robb JP, Andermann F (September 1969). “Familial agenesis of the cerebellar vermis. A syndrome of episodic hyperpnea, abnormal eye movements, ataxia, and retardation”. Neurology 19 (9): 813–25. PMID 5816874.
4.Vincent Cantagrel,1,17 Jennifer L. Silhavy, et al (2008)”Mutations in the Cilia Gene ARL13B Lead to the Classical Form of Joubert Syndrome” The American Journal of Human Genetics,Published online 2008 August 1. doi: 10.1016/j.ajhg.2008.06.023.
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Personalised Approach To Tackling Breast Cancer Studied

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Invasive ductal carcinoma of the breast. H&E s...

Invasive ductal carcinoma of the breast. H&E stain Image via Wikipedia

Introduction

Improving quality of life and potentially keeping the cancer under control for a longer period of time are goals of a new clinical trial at the cancer center’s TGen Clinical Research Services, a partnership of Scottsdale Healthcare and the Translational Genomics Research Institute (TGen).

“Many are living with refractory (cancer that has not responded to treatmnent), or advanced, breast cancer that has not responded or continues to grow despite standard treatments,” explains Nurse Practitioner Gayle Jameson, principal investigator.

The pilot study is supported by the Side-Out Foundation, a group founded by volleyball enthusiasts to help wage war on breast cancer.Women or men with advanced breast cancer that has progressed through three prior treatments are eligible for the trial, available in the western U.S. only.The new study, managed by TGen Drug Development (TD2), is open to a total of 25 patients at only two sites, the Virginia G. Piper Cancer Center at Scottsdale Healthcare and Fairfax Northern Virginia Hematology Oncology.

Approach

Biopsied tissue will be analyzed for unique characteristics and abnormal genes in cancer cells, which are then targeted for treatment with FDA-approved anticancer medications. “We may discover that a tumor has a gene mutation that responds to a drug not typically used in a ‘one-size-fits-all’ approach,” explains Jameson.

“What we are doing here is precisely matching a treatment to a specific type of cancer cell mutation and abnormal protein signaling pathways that may activate cancer cell growth. The patient would then be treated with one or more medications based on the information provided by the analyses.”

Researchers call the Side-Out study the “next generation of breast cancer treatment,” expanding on what was learned about molecular profiling in an earlier clinical trial at the Virginia G. Piper Cancer Center.

Results of the earlier trial, known as the Bisgrove Study, showed that molecular profiling can identify specific treatments that help keep cancer in check for significantly longer periods, and in some cases even shrinking tumors. Clinical trials at the cancer center are administered by the Scottsdale Healthcare Research Institute.

Disscussion

This is a great step forword in the whole area of personalised medicine which identifies charactertistiscs of disease that are specific to different people.These characteritics can then be targeted more accuratly using the correct medication.Although this is approach is used to some degree in many treatments e.g. identifying hormone receptive breat cancers from those that are not ,this takes that approach to a whole new level.

About TGen

The Translational Genomics Research Institute (TGen) is a non-profit 501(c)(3) organization focused on developing earlier diagnostics and smarter treatments.

Translational genomics research is a relatively new field employing innovative advances arising from the Human Genome Project and applying them to the development of diagnostics, prognostics and therapies for cancer, neurological disorders, diabetes and other complex diseases.

References:

http://www.tgen.org/index.cfm

Retrieved March 14, 2010, from http://www.sciencedaily.com­ /releases/2010/03/100311151722.htm

Other Interesting Articles:

A look at the treatment benefits of differentiating between characteristics of recurrent breat cancer from those of the original cancer :http://www.sciencedaily.com/releases/2009/03/090318211238.htm

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