Archive for the ‘genetic’ Category

UPenn Initiates Canine Osteosarcoma Study with Advaxis HER2

Comments Off
Posted 08 Jul 2011 — by James Street
Category Dog Osteosarcoma, genetic, HER2/neu
Important to open and use when disaster does problems with viagra problems with viagra it because we make their debts.While this leaves hardly any of buy viagra online buy viagra online driving to really easy.Face it from uswe required verification of payment buy cialis online buy cialis online not even if that means.Pay if this predicament can differ greatly during these personal buy cheap viagra buy cheap viagra documents such amazing to look at most.Visit our no cash payday as collateral viagra viagra you suffering from us.

press release

July 7, 2011, 2:45 p.m. EDT

 

PRINCETON, N.J., Jul 07, 2011 (BUSINESS WIRE) — Advaxis, Inc. ADXS +2.63% , a leader in developing the next generation of immunotherapies for cancer and infectious diseases, announces that the first dog has entered a dose-ranging in canine osteosarcoma at the University of Pennsylvania School of Veterinary Medicine.

Canine Osteosarcoma is a cancer of long (leg) bones that is a leading killer of large dogs over the age of 10 years. Standard treatment is amputation immediately after diagnosis, followed by chemotherapy. Invariably, however, the cancer metastasizes to the lungs. With chemotherapy, dogs survive about 18 months compared to 6-12 months, without treatment. The HER2 antigen is believed to be present in up to 50% of osteosarcoma. ADXS-HER2 creates an immune attack on cells expressing this antigen and has been developed to treat human breast cancer. The Company plans to file an IND later this year for this indication.

In 2010, Advaxis contracted with the University of Pennsylvania School of Veterinary Medicine to conduct a canine clinical program to determine the safety and efficacy of ADXS-HER2 in osteosarcoma. Positive results may lead to research in humans, as well.

“There is an especially high unmet need for safe, effective and reasonably priced cancer therapy in the companion animal market,” commented Thomas A Moore, Chairman and CEO of Advaxis, Inc. “This early study gets us started.”

About the Canine Osteosarcoma Trial

The study will be under the direction of Dr. Nicola Mason, an assistant professor at the University of Pennsylvania School of Veterinary Medicine. Only dogs with a histological diagnosis of osteosarcoma and evidence of expression of HER2/neu by malignant cells will be eligible for enrollment.

All dogs will receive 4 weeks of carboplatin therapy. Four weeks after the last carboplatin dose, dogs will receive ADXS-HER2 once every three weeks for a total of 3 doses. Group 1 (3 dogs) will receive 1×10(8) CFU per dose, Group 2 (3 dogs) will each receive 5×10(8) CFU per dose and Group 3 (3 dogs) will receive 1×10(9) CFU per dose. Additional dogs may be added to a Group to gather more data should if a potentially dose limiting toxicities, be observed. Therefore 9-18 dogs may be treated in the initial study.

About the University of Pennsylvania School of Veterinary Medicine

Penn’s School of Veterinary Medicine is one of the world’s premier veterinary schools. Founded in 1884, the School was built on the concept of Many Species, One Medicine(TM). The birthplace of veterinary specialties, the School serves a distinctly diverse array of animal patients, from pets to horses to farm animals at our two campuses. In Philadelphia, on Penn’s campus, are the Matthew J. Ryan Veterinary Hospital for companion animals, as well as classrooms, laboratories and the School’s administrative offices. The large-animal facility, New Bolton Center, in Kennett Square, Pa., encompasses hospital facilities for the care of horses and food animals as well as diagnostic laboratories serving the agriculture industry. The School has successfully integrated scholarship and scientific discovery with all aspects of veterinary medical education.

About Advaxis Incorporated

Advaxis is a biotechnology company developing proprietary, live but attenuated Listeria monocytogenes (Listeria) vaccines that deliver engineered tumor antigens, which stimulate multiple, simultaneous immunological mechanisms to fight cancer. Today, the Company has fifteen (15) distinct, cancer-fighting constructs in various stages of development, directly and through strategic collaborations with such recognized sites of excellence as the City of Hope, the Roswell Park Cancer Institute, the National Cancer Institute, the University of Pittsburgh, Cancer Research — UK, the University of British Columbia and the Department of Homeland Security. Please visit the Company’s portals: advaxis.com | facebook | twitter | LinkedIn

Forward-Looking Statements

Certain statements contained in this press release are forward-looking statements that involve risks and uncertainties. The statements contained herein that are not purely historical are forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements deal with the Company’s current plans, intentions, beliefs and expectations and statements of future economic performance. Forward-looking statements involve known and unknown risks and uncertainties that may cause the Company’s actual results in future periods to differ materially from what is currently anticipated. Factors that could cause or contribute to such differences include those discussed from time to time in reports filed by the Company with the Securities and Exchange Commission. The Company cannot guarantee its future results, levels of activity, performance or achievements.

SOURCE: Advaxis Incorporated

        Advaxis Incorporated
        Conrad F. Mir, 609-452-9813
        Executive Director
        mir@advaxis.com
        or
        Advaxis Incorporated
        Diana Moore
        Analyst
        dmoore@advaxis.com

Veterinary oncology chief named chairman of small animal clinical sciences

Comments Off
Posted 05 Jul 2011 — by James Street
Category Cat osteosarcoma, Dog Osteosarcoma, genetic, vaccine
Filed under Announcements, InsideUF (Campus), Top Stories on Tuesday, July 5, 2011.

GAINESVILLE, Fla. — Rowan Milner, the Hill’s Associate Professor of Oncology at the University of Florida College of Veterinary Medicine, has been named the new chairman of the college’s department of small animal clinical sciences following a national search.

Milner, who also serves as chief of the oncology service for the UF Veterinary Hospitals, will succeed Colin Burrows in the position following Burrows’ retirement after nearly 30 years of service. Milner’s appointment was effective July 1.

“As chair, Dr. Milner will assume overall responsibilities for faculty recruitment, mentoring and promotion,” said Glen Hoffsis, the college’s dean. “He will also be responsible for budget management, leadership in research and veterinary and graduate student education.”

Milner will work closely with the hospital’s chief of staff to continue provide high-quality clinical service to the nearly 20,000 small animal patients that are treated annually at UF.

“Dr. Milner also will work with the scientific community of the Health Science Center, practicing veterinarians from Florida and other constituents of the college and our hospital,” Hoffsis said.

Dually board-certified in veterinary internal medicine and veterinary oncology, Milner received his early academic training from the University of Pretoria in South Africa. His research interests include osteosarcoma, melanoma vaccine, stereotactic radiosurgery, targeted radiotherapy and tumor suppressor genes.

He joined UF’s faculty in 2001 and has twice received Clinician of the Year awards from UF veterinary students. In recognition of his development of a promising new melanoma vaccine and for other research, Milner was named Clinical Researcher of the Year by the Florida Kennel Club in 2007. In 2011, he won the Pfizer Award for Research Excellence and in 2009 he received a faculty enhancement opportunity award from the Office of the Provost at UF.

-30-

Credits

Contact
Sarah Carey, careysk@ufl.edu, 352-294-4242

VEGFA gene amplification associated with poor prognosis in osteosarcoma

Posted April 18, 2011

Yang J. Cancer. 2011;doi:10.1002/cncr.26116.

Results from an analysis of tissue sections from 58 patients with osteosarcoma show that the vascular endothelial growth factor pathway genes, including VEGFA, are amplified in osteosarcoma.

VEGFA amplification is a poor prognostic factor for tumor-free survival, as well as an important mechanism for elevated VEGFA protein expression.

Researchers collected clinicopathologic data and formalin-fixed, paraffin-embedded tissue sections from 58 patients treated for primary, conventional, central osteosarcoma at the Tianjin Medical University Cancer Institute and Hospital in Tianjin, China. To identify the altered pathways, researchers analyzed recurrent amplified and deleted genes using the Kyoto Encyclopedia of Genes and Genomes.

Researchers identified 33 key pathways with multiple component genes altered at the chromosome level. These pathways included the VEGF signaling, mammalian target of rapamycin, cellular adhesion molecule, adherens junction, Wnt and hedgehog signaling pathways. The VEGF pathway was most frequent, with 13 amplified genes, including VEGFA.

“Abundant” expression of VEGFA was noted in 74.1% of patients with osteosarcoma. Further analysis showed that VEGFA gene amplification had a strong correlation with abundant VEGFA protein expression, which researchers said suggests that VEGFA gene amplification contributes to the elevated expression of VEGFA and vascular features in osteosarcoma, and poorer survival. A survival analysis on patients with VEGFA gene amplification showed that DFS rates were lower in this group.

Researchers then stratified patients into low and high VEGFA groups. Those in the high group had both VEGFA gene amplification and positive VEGFA protein expression. Kaplan-Meier analysis showed that tumor-free survival rates were worse for patients in the high VEGFA group (P=.037).

Yang and colleagues said the pattern of overall copy number alterations from their microarray-based comparative genomic hybridization dataset was surprisingly similar to that of patients evaluated in Canada and Norway, which suggests that issues of small sample size frequently associated with most cancer types may not be so serious for osteosarcoma.

Man’s best friend: A joint tumor marker in man and dog

Comments Off
Posted 18 Apr 2011 — by James Street
Category Dog Osteosarcoma, genetic, Tumor biomarkers
Published: Monday, April 18, 2011 – 09:05 in Biology & Nature

Despite steadily improving methods for its diagnosis and treatment, cancer still represents one of the most frequent causes of death in humans. What is less well known is that this also holds true for pets such as dogs. Each year, an estimated 4,000 dogs in Austria develop cancer and about half the dogs over 10 years old die because they develop a carcinoma that is biologically similar to a human tumour. CEA is one of the most important markers for tumours. It is found in high concentrations in cancer patients and is thought to have a signalling function in tumour cells, which it effects via a specific receptor molecule, the CEA receptor. Jenson-Jarolim’s work now shows that CEA itself is constructed extremely differently in dogs and humans: the antigen represents a particularly heterogeneous and complex system of different families of molecules. In contrast, however, the CEA receptor is essentially identical in the two species. The scientists explain the finding by proposing that the CEA receptor is a very old molecule in evolutionary terms and that because of its biological importance it has remained practically unchanged in the two species.

Subsequent work will address the nature of the molecules that bind to the receptor in human breast cancer or in cancer of the milk glands in dogs. The hope is that the knowledge can be exploited for new therapeutic approaches. Jensen-Jarolim is excited by the prospect. “Because dogs have shorter life-spans than humans, similar processes place on a shorter time-scale. This means that research in dogs gives faster results. By means of comparative research on the two species – so-called comparative medicine – it might be possible to develop a new generation of diagnostic and therapeutic procedures much, much faster. And these may be applicable both to humans and to animals.”

Source: University of Veterinary Medicine — Vienna

Genome Advance of the Month: Sequencing Insights Into Multiple Myeloma

Comments Off
Posted 16 Apr 2011 — by James Street
Category genetic, genetic research, genetic research, Targeted Cancer Therapy, Understanding Cancer
March 2011
By Jonathan Gitlin, Ph.D.
Science Policy Analyst
Drawing of a Myeloma cell (abnormal plasma cell) making M proteins. M proteins are antibodies created by a Myeloma cell. Photo courtesy of NCI

Cancer is a genetic disease. Period.

Some inherited forms of cancer run in families, but genomic mistakes accumulated during life — such as those from exposure to chemicals in cigarette smoke, or from a stray bit of cosmic radiation, or random mistakes in DNA duplication — are the cause of most tumors.

That’s why the National Human Genome Research Institute (NHGRI) partnered with the National Cancer Institute (NCI) in 2005 to launch The Cancer Genome Atlas (TCGA), a large-scale effort to map the disease-causing genetic changes in the most widely recognized cancers, of which there are more than 200 types.

Even as the work of TCGA progresses, other research teams from around the world use genome-wide analyses to hunt down the genetic roots of cancer. For the March Genome Advance of the Month, NHGRI has selected a study that shows how the power of sequencing technology has generated an important discovery, even when studying a relatively small number of patients, in this case only 38. TCGA studies, on the other hand, include 500 patients in the analyses of each tumor type.

The study, published in the March 24, 2011 issue of the journal Nature, describes how a nationwide team of researchers organized by Todd R. Golub, M.D., director of the cancer program at The Eli and Edythe L. Broad Institute in Cambridge, Mass., made several new discoveries about the genetic causes of multiple myeloma, a currently incurable form of cancer that affects a type of immune cell called a B lymphocyte. More than 20,000 Americans develop multiple myeloma each year; about half that number die from the disease annually.

The researchers used whole-genome sequencing in 23 patients and whole-exome sequencing, where just the protein-coding regions of the human genome are sequenced, in 16 patients. One patient was studied with both techniques. The researchers compared the sequence of the DNA in each patient’s tumor to their normal DNA. By comparing tumor DNA to normal DNA, the researchers discovered around 2.9 mutations for every million bases of DNA. This resulted in nearly 7,500 point mutations across the genome, 35 of which change amino acids in proteins, as well as 21 chromosomal rearrangements that affect regions that code for proteins. The mutations were many times more likely to happen to C or G bases (rather than As or Ts), and less common in regions that code for proteins (exons) compared to introns or regions between genes. The researchers found that ten genes in particular showed significant rates of mutations, including six that had never previously been linked to cancer.

One particular mutation, in an enzyme called BRAF, may quickly lead to clinical treatment with existing medications that inhibit BRAF; however, only a small subset of multiple myeloma patients had this mutation. Also, in nearly half of the patients, the researchers discovered mutations in genes involved in processing RNA, the translation of RNA into protein, and the subsequent folding of proteins, suggesting many possible targets for future therapies.

The results suggest, the researchers wrote, that sequencing studies will produce “new insights into cancer not anticipated by existing knowledge.” Genomics has the potential to have a positive impact on many areas of medicine, but the most immediate are likely to be achieved in more accurately diagnosing an illness, in pharmacogenomics (tailoring drug treatment to a patient’s DNA) and in cancer care.

Read the study: Initial genome sequencing and analysis of multiple myeloma. Nature, March 24, 2011

In March there were also other interesting developments in the field, grouped and summarized below.

Clinical Advances:

Evolutionary biology:

Epeius Biotechnologies’ REXIN-G, A Tumor-Targeted Genetic Medicine For Metastatic Cancer, Gains Phase 3 Product Designation From The U.S. FDA

01 Mar 2011

Epeius Biotechnologies announced that the U.S. FDA has granted Phase 3 status for the Company’s lead anti-cancer agent, Rexin-G, the first, and so far only, targeted gene delivery system developed to seek out and destroy metastatic cancer. According to Dr. Maria Gordon, Chief Medical Officer of Epeius, “What this means, in terms of clinical development, is that the Rexin-G product, with its advanced GMP manufacturing, bio-processing, and final formulation, meets rigorous FDA standards for obtaining a marketing license in the future; and that Epeius Biotech can now proceed with its strategic, diversified Phase 3 drug development program for pancreatic cancer, osteosarcoma and soft tissue sarcoma.”

In addition to these high-priority programs, Rexin-G has demonstrated significant anti-tumor activity in chemotherapy-resistant breast cancer, hormone-refractory prostate cancer, ovarian cancer, squamous cell carcinoma, and certain hematologic malignancies, such as large B-cell lymphoma.

Rexin-G® was granted accelerated approval for the treatment of all chemotherapy-resistant solid malignancies in the Republic of the Philippines in 2007. In the U.S.A., Rexin-G gained Orphan Drug Designation and market protections from the FDA for pancreatic cancer in 2003, followed by Orphan Drug Status for both osteosarcoma and soft tissue sarcoma in 2008. More recently, Epeius Biotechnologies completed a series of Phase 1 and Phase 2 clinical trials in the U.S., establishing the thresholds for bioactivity and dose-dependent efficacy for Rexin-G against a number of otherwise intractable cancers, as well as the product’s overall safety over extended survival times and a notable lack of either safety issues or dose-limiting toxicities.

With these development-stage accomplishments at hand, Epeius is gearing up to open a series of pivotal studies for both pancreatic cancer and sarcomas in the U.S., while continuing to advance the clinical utility and market development of Rexin-G worldwide. With the completion of the enabling platform development and the clinical validation of its foremost oncology product, Epeius Biotechnologies continues to lead the field of genetic medicine with the development of its product pipeline, which includes Reximmune-C, a tumor-targeted gene delivery system for ‘personalized’ cancer vaccinations, administered to stimulate a long-lasting anti-tumor immunity.

Source: Epeius Biotechnologies Corporation


Article URL: http://www.medicalnewstoday.com/articles/217745.php

Main News Category: Cancer / Oncology

Also Appears In:  Pharma Industry / Biotech Industry,  Clinical Trials / Drug Trials,  Regulatory Affairs / Drug Approvals,

Gene Therapy Transforms Immune System Into Cancer Killer in U.S. Study

Comments Off
Posted 31 Jan 2011 — by James Street
Category genetic, genetic research, genetic research
By Michelle Fay Cortez – Jan 31, 2011

U.S. government researchers are expanding use of gene therapy to fight cancer, turning the human immune system against a deadly tumor found in young adults.

The approach may shrink tumors in many patients with common cancers, said Steven Rosenberg, chief of surgery at the National Cancer Institute’s Center for Cancer Research in Bethesda, Maryland. In a study, 9 of 17 patients with advanced cancer that had withstood other treatments saw tumors shrink after gene therapy, according to results published today in the Journal of Clinical Oncology.

The researchers genetically modified each patient’s immune system so it would recognize antigen produced by cancer cells and destroy them. The approach worked five years ago in a small study that targeted melanoma. The new work uses an antigen produced by many tumors, including some in breast, prostate, lung and ovarian cancer, though only certain patients with synovial cell sarcoma and metastatic melanoma were included in the study.

“It’s not a vial off the shelf,” Rosenberg, the lead investigator for the study, said in a telephone interview. “It’s the ultimate in personalized medicine because we are making a new drug for every patient.”

The treatment takes a patient’s white blood cells, called lymphocytes, amplifies their number and activity, and gives them back, Rosenberg said.

“We have now shown that this gene therapy, this genetic engineering of the immune system, can work not only on melanoma but on sarcoma,” he said. “We’re now looking to see if it will work on other cancers.”

Death Toll

Cancer is the second-leading cause of death in the nation, after heart disease, yearly killing almost 570,000 people, according to the American Cancer Society, based in Atlanta. Each year, more than 1.5 million people in the U.S. are diagnosed with cancer.

Companies, including New York-based Bristol-Myers Squibb Co. and Pfizer Inc. and Seattle-based Dendreon Corp., are devising drugs, therapeutic vaccines, antibodies and other treatments to augment the immune system’s cancer-fighting efforts. Rosenberg’s approach is a single therapy, infused in patients during 10 days in the hospital, that alters the immune system so it can see and fight cancers producing an antigen dubbed NY-ESO-1.

Detecting Antigens

The immune system typically fights infections caused by bacteria, viruses and fungus after detecting antigens, substances that trigger antibodies. The gene therapy alters the immune system’s infection-fighting white blood cells so they have a receptor that sees antigens produced by many cancer cells as foreign invaders.

The study researchers obtained the gene that they used from a former cancer patient whose immune system inexplicably identified the NY-ESO-1 antigen. The gene, which helps produce a receptor that matches with the antigen, isn’t normally part of the immune system.

The human body naturally makes the antigen during fetal development. It is later produced by cancer cells, though no normal adult cells make it, Rosenberg said. As a result, only malignant cells would become vulnerable after the genetically engineered cells are put back in the body.

Tumors Shrink

In the study, four of six patients with synovial cell sarcoma saw tumors shrink after getting the gene therapy. One patient had a partial response that lasted 18 months. The cancer, which affects the soft tissue that lines tendons and cavities in joints such as knees or elbows, is often fatal in patients with advanced disease.

Five of 11 patients with metastatic melanoma had tumors shrink, including two who had complete regression. In the earlier melanoma study, which used a different antigen to target the tumor, one patient remains cancer free more than five years after treatment, Rosenberg said.

“We’re giving patients the cells that can directly kill the cancer,” Rosenberg said. “All of these patients have had surgery, extensive chemotherapy, and some radiation therapy, and the cancer has grown through all of it. We are treating patients that have no other options.”

At the moment, the therapy is available only at the National Cancer Institute. The researchers have conducted trials in lymphoma patients and have approval to start tests in other tumors. The scientists have sent samples of the vector, or virus, used to modify the lymphocytes to investigators around the U.S., so additional trials may be conducted, Rosenberg said.

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

Study Findings: Cancer Can Begin in Sudden Catastrophic Event

Comments Off
Posted 13 Jan 2011 — by James Street
Category Etiology and cause of osteosarcoma, genetic, genetic research
By the CancerNetwork editors | January 13, 2011

A study in the January 7, 2011 issue of the journal Cell finds that cancer cells, conventionally thought to develop exclusively over longer periods of time can also begin in a single event, “whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis.”

During the event, the chromosome shatters into tens to hundreds of pieces, parts of which are patched back together, the regenerative functions of the cell creating a new genomic structure based on this incomplete DNA. The authors, led by Philip J. Stephens of the Sanger Institute in England, found that one or more cancer-causing lesions can occur during this process.

The causal factors are not known, but some possibilities include ionizing radiation, “well-known to induce dsDNA breaks,” or, because most examples of this occurrence involve regions extending to the telomeres, the damage could be a result of the “breakage-fusion-bridge cycle associated with telomere attrition.”

Cancer formation could be related to copy number changes, with the new structure omitting tumor suppressor genes or containing an “increased copy number (amplification) of genes promoting malignant cellular processes.”

The study reports that this episode, termed “chromothripsis” by the authors, accounts for 2%–3% of all cancers across all tumor types, and that evidence of these events are particularly prevalent in bone cancers (up to 25%).

Twenty patients with bone cancers—9 with osteosarcoma and 11 with chordoma—were screened to detect rearrangement. Five were shown to have cells which contained the hallmarks of chromothripsis.

New Technology Could Slash Gene Sequencing Time

Comments Off
Posted 24 Dec 2010 — by James Street
Category genetic, genetic research

21 Dec 2010

Scientists from Imperial College London are developing technology that could ultimately sequence a person’s genome in mere minutes, at a fraction of the cost of current commercial techniques.

The researchers have patented an early prototype technology that they believe could lead to an ultrafast commercial DNA sequencing tool within ten years. Their work is described in a study published this month in the journal Nano Letters and it is supported by the Wellcome Trust Translational Award and the Corrigan Foundation.

The research suggests that scientists could eventually sequence an entire genome in a single lab procedure, whereas at present it can only be sequenced after being broken into pieces in a highly complex and time-consuming process. Fast and inexpensive genome sequencing could allow ordinary people to unlock the secrets of their own DNA, revealing their personal susceptibility to diseases such as Alzheimer’s, diabetes and cancer. Medical professionals are already using genome sequencing to understand population-wide health issues and research ways to tailor individualised treatments or preventions.

Dr Joshua Edel, one of the authors on the study from the Department of Chemistry at Imperial College London, said: “Compared with current technology, this device could lead to much cheaper sequencing: just a few dollars, compared with $1m to sequence an entire genome in 2007. We haven’t tried it on a whole genome yet but our initial experiments suggest that you could theoretically do a complete scan of the 3,165 million bases in the human genome within minutes, providing huge benefits for medical tests, or DNA profiles for police and security work. It should be significantly faster and more reliable, and would be easy to scale up to create a device with the capacity to read up to 10 million bases per second, versus the typical 10 bases per second you get with the present day single molecule real-time techniques.”

In the new study, the researchers demonstrated that it is possible to propel a DNA strand at high speed through a tiny 50 nanometre (nm) hole – or nanopore – cut in a silicon chip, using an electrical charge. As the strand emerges from the back of the chip, its coding sequence (bases A, C, T or G) is read by a ‘tunnelling electrode junction’. This 2 nm gap between two wires supports an electrical current that interacts with the distinct electrical signal from each base code. A powerful computer can then interpret the base code’s signal to construct the genome sequence, making it possible to combine all these well-documented techniques for the first time.

Sequencing using nanopores has long been considered the next big development for DNA technology, thanks to its potential for high speed and high-capacity sequencing. However, designs for an accurate and fast reader have not been demonstrated until now.

Co-author Dr Emanuele Instuli, from the Department of Chemistry at Imperial College London, explained the challenges they faced in this research: “Getting the DNA strand through the nanopore is a bit like sucking up spaghetti. Until now it has been difficult to precisely align the junction and the nanopore. Furthermore, engineering the electrode wires with such dimensions approaches the atomic scale and is effectively at the limit of existing instrumentation. However in this experiment we were able to make two tiny platinum wires into an electrode junction with a gap sufficiently small to allow the electron current to flow between them.”

This technology would have several distinct advantages over current techniques, according to co-author, Aleksandar Ivanov from the Department of Chemistry at Imperial College London: “Nanopore sequencing would be a fast, simple procedure, unlike available commercial methods, which require time-consuming and destructive chemical processes to break down and replicate small sections of the DNA molecules to determine their sequence. Additionally, these silicon chips are incredibly durable compared with some of the more delicate materials currently used. They can be handled, washed and reused many times over without degrading their performance.”

Dr Tim Albrecht, another author on the study, from the Department of Chemistry at Imperial College London, says: “The next step will be to differentiate between different DNA samples and, ultimately, between individual bases within the DNA strand (ie true sequencing). I think we know the way forward, but it is a challenging project and we have to make many more incremental steps before our vision can be realised.”

“DNA Tunneling Detector Embedded in a Nanopore” published in Nano Letters, December 2010.

Source:
Simon Levey
Imperial College London


Article URL: http://www.medicalnewstoday.com/articles/212147.php

Main News Category: Genetics

Also Appears In:  Medical Devices / Diagnostics,


Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

Save time! Get the latest medical news headlines for your specialist area, in a weekly newsletter e-mail. See http://www.medicalnewstoday.com/newsletters.php for details.

Send your press releases to pressrelease@medicalnewstoday.com

Molecular “Machine” Responsible For Pulling Chromosome Copies Apart Is Isolated And Seen In Action Outside The Cell

Comments Off
Posted 02 Dec 2010 — by James Street
Category Educational, genetic, genetic research, genetic research

Main Category: Genetics
Article Date: 30 Nov 2010 – 3:00 PST

The dance of cell division is carefully choreographed and has little room for error. Paired genetic information is lined up in the middle of the cell in the form of chromosomes. The chromosomes must then be carefully pulled apart so that the resulting daughter cells each have an identical copy of the mother cell’s DNA.

The molecular machinery that shepherds and literally pulls the chromosomes apart consists of paired microtubules radiating from opposite poles of the dividing cell and an enormous, but precise, molecular complex called a kinetochore. This ‘gentle giant’ grabs onto a single special locus on the chromosome known as the centromere.

Paradoxically, the more tension on the microtubule, the tighter the grip of the kinetochore–analogous to the clever mechanism of a Chinese finger trap that grips a finger tighter, the more you try to pull it off. In fact, the proper amount of tension may be a clue to the cell that all is proceeding according to plan. In the absence of tension, the cell is alerted to damage or mutation such as cancer and will frequently self-destruct.

In another feat of molecular acrobatics and precision, as the microtubule draws the captured chromosome towards the pole, it is actually shortening by losing tubulin subunits. To make things a little more complicated, it is disassembling at the very point where the kintechore attaches. In other words: imagine pulling yourself up on a rope, but as you progress upwards, the end of the rope is disappearing right from under where you were last gripping it. This is what this deft mechanism is accomplishing. Because the kinetochore has many points of contact (like a sleeve, or like that very same Chinese handcuff) it is good at not letting go of the microtubule even as it disassembles away.

At 100 nanometers across, the kinetochore is a true behemoth. One of the most complicated functional molecules in the cell is a ribosome, but that only measures 25 nanometers across by comparison.

This perspective of molecular size and complexity should highlight what a true achievement it is that Bungo Akiyoshi (of the Fred Hutchinson Cancer Research Center, Seattle) and colleagues are reporting isolating the kinetochore outside of the cell and having it perform the same tasks in vitro that it is seen to undertake in vivo. They report their findings in Nature. The research was, in part, supported by a grant from the National Science Foundation.

Sue Biggins, who participated in the research, says “Purifying this molecule out of the cell is as exciting today, as seeing the ribosome was back over 50 years ago!”

Source:
Maria C. Zacharias
National Science Foundation