Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED ON 6/17/2013
UCSC Designing Social Network-type Model for Analyzing Cancer Data
NEW YORK (GenomeWeb News) – Seeking to make the masses of cancer sequence data that is being generated more useful for researchers, investigators at University of California, Santa Cruz, plan to use a $3.5 million grant from the National Cancer Institute to create a new platform for organizing and accessing these data.
The UCSC group plans to create a method for making the raw sequence information in repositories like the university’s Cancer Genomics Hub more useful for investigators seeking to make clinical predictions about how cancer mutations respond to drugs, for example.
The aim of the project will be to develop a new database called the Biomedical Evidence Graph, or BMEG, which will use a graph database structure, like Facebook does, to enable swift access to complex and interconnected datasets.
Principal investigator Joshua Stuart, a UCSC associate professor of engineering, likened the difficulty for many investigators of using raw sequence data to average computer users trying to work directly with binary code.
“Your web browser doesn’t understand zeros and ones. There are layers and layers of software programs between that and what you see on a web page. We need to do the same thing for DNA sequences to reach the higher levels of interpretation needed for scientific discovery,” Stuart said in a statement.
Stuart said that a platform similar to what social networks like Facebook use offer a “natural way” to represent data from tumor samples based upon the connections between their molecular profiles.
CGHub, which launched last year to house data from The Cancer Genome Atlas consortium and similar projects, holds thousands of genome sequences from individual patients and access is highly controlled and limited to approved projects.
BMEG, however, will not require such security because it will host higher-level data from analyses of the raw genome sequencing. This will enable a broader group of investigators to use and analyze these datasets without having to download massive files to their computers.
“TCGA researchers have built a lot of great tools for data analysis, and we need to get those installed in the BMEG so the rest of the world can engage in that higher level analysis,” Stuard said. “The idea is to build a shared knowledge base and create a playground where lots of researchers can interact, test their algorithms, and compare results.”
The BMEG will be located with the CGHub servers at the San Diego Supercomputer Center, and investigators will be able to run their analyses as apps on the BMEG, UCSC said.
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SOURCE
http://www.genomeweb.com//node/1242591?hq_e=el&hq_m=1590835&hq_l=3&hq_v=e1df6f3681
Five3, maker of cancer genomics software, takes off from UCSC labs
October 29, 2012 | By Ryan McBride
Recent software applications have enabled scientists to analyze cancer genomic data to track molecular changes in cells, spotting some of the triggers that cause tumors to grow. Led by CEO and co-founder Steve Benz, Five3 Genomics plans to sell its cancer genomics software to healthcare companies and pharmaceutical firms. Drugmakers could use the company’s software to discover new targets for cancer therapies, while hospitals could use the technology to put patients on existing drugs that home in on the molecular triggers of their cancer.
Benz and his fellow co-founders have a crack group of bioinformatics and biotech experts to help guide their startup. They’ve called on their UCSC mentors, David Haussler and Joshua Stuart. Haussler’s lab has participated in some of the most pioneering efforts in genomics over the past couple of decades, including the Human Genome Project that raced to decode an entire human genome. Also, Dr. Patrick Soon-Shiong, who has made billions of dollars in biotech, is serving as a scientific adviser.
“We’re working with academic collaborators to build out the platform and starting conversations with pharmaceutical companies and insurance companies,” Benz, who recently wrapped up his doctorate at UCSC, told the Santa Cruz Sentinel newspaper. “It’s a great opportunity to be able to take this technology and commercialize it so that it can be used to help patients.”
SOURCE:
http://www.fiercebiotechit.com/story/five3-maker-cancer-genomics-software-takes-ucsc-labs/2012-10-29
UCSC grad students launch cancer genomics company in Santa Cruz
By Sentinel Staff Report
Santa Cruz Sentinel
Posted: 10/24/2012 04:11:37 PM PDT
SANTA CRUZ — The co-founders of Five3 Genomics, a new biotech company based in Santa Cruz, are former graduate students in the Baskin School of Engineering at UC Santa Cruz, where they helped develop innovative cancer genomics software.
Their company, which has signed a license agreement with UCSC, offers software and services for cancer researchers, pharmaceutical companies, and health-care organizations. Its goal is to provide the data processing and analysis required for personalized cancer therapy, in which treatments are matched to the specific genetic aberrations found in an individual patient’s cancer cells.
“We’re working with academic collaborators to build out the platform and starting conversations with pharmaceutical companies and insurance companies,” said CEO Steve Benz, who completed his doctorate in bioinformatics this year. “It’s a great opportunity to be able to take this technology and commercialize it so that it can be used to help patients.”
In addition to Benz, the co-founders of Five3 Genomics include Chief Technical Officer Zachary Sanborn and Chief Scientific Officer Charles Vaske. All three of them worked as graduate students with UC Santa Cruz bioinformatics experts David Haussler and Joshua Stuart, who are doing pioneering work in the field of cancer genomics. Haussler, a professor of biomolecular engineering and Howard Hughes Medical Institute investigator, said that Benz, Sanborn, and Vaske were “brilliant gradstudents.”
“Working at UCSC they were exposed to the cutting edge in computational genomics,” Haussler said. “They played a key role in developing our cancer genomics program.”
Vaske, who earned his doctorate in 2009, and Benz were lead developers of a software program from Stuart’s lab called Paradigm. Stuart, a professor of biomolecular engineering, has been a close collaborator with Haussler on cancer genomics projects, including The Cancer Genome Atlas funded by the National Institutes of Health and two cancer research “Dream Teams” funded by Stand Up To Cancer and other organizations.
Paradigm, one of the core technologies for Five3 Genomics, is used to understand which molecular pathways are affected by the genetic changes in a patient’s cancer cells. This information can be used in a clinical setting to guide therapeutic decisions and by pharmaceutical companies to identify new targets for drug development.
“On the pharmaceutical side, we can provide indications for new uses for drugs that are already out there, as well as identify targets for new drugs,” Benz said.
Sanborn, who will finish his doctorate this year, worked in Haussler’s lab on a DNA sequence analysis program called BamBam, which is used to identify the genetic changes in cancer cells. Sanborn and Benz also contributed to the development of the UCSC Cancer Genome Browser in Haussler’s lab.
The scientific advisers for Five3 Genomics include Haussler and Stuart, as well as Dr. Patrick Soon-Shiong, a surgeon, medical researcher, and biotechnology entrepreneur, and Dr. Margaret Tempero, deputy director and director of research programs at the UCSC Helen Diller Family Comprehensive Cancer Center.
“It’s particularly gratifying to see this UCSC research transition to a commercial product, so these cutting-edge techniques can begin to benefit the public as quickly as possible,” said Bruce Margon, vice chancellor for research at UCSC.
SOURCE:
http://www.santacruzsentinel.com/localnews/ci_21846767
Biotech billionaire’s supercomputer cuts cancer analysis to 47 seconds
October 4, 2012 | By Ryan McBride
Dr. Patrick Soon-Shiong, a surgeon and biotech mogul, has spotlighted a supercomputer-based system and network to rapidly transfer and analyze cancer genetic data in mere seconds as opposed to the weeks or months of previous approaches. The supercomputer crunches genetic data from a tumor with results on abnormalities in 47 seconds, and the high-speed fiber-optic network Soon-Shiong has championed transfers samples in shy of 18 seconds, according to an announcement Wednesday.
Soon-Shiong’s L.A.-based company NantHealth has joined forces with Verizon, Intel, Hewlett-Packard, Blue Shield of California and other players to advance a national system to enable rapid sharing of genomic information among cancer doctors, aiding physicians in making the right call on treatments for patients based on the characteristics of their tumors. It’s a big deal because lack of such information contributes to misdiagnoses.
Via NantHealth and other vehicles, Soon-Shiong has worked on integrating a variety of digital technologies to revolutionize scientific research and medicine. As Reuters reports, he’s poured more than $400 million from his estimated fortune of more than $7 billion into building the fiber-optic network. His nonprofit is working on connecting sequencing centers, medical research hubs and hospitals to the network to create an infrastructure for these groups to share data from big science endeavors such as The Cancer Genome Atlas.
Soon-Shiong built most of his fortune with the sales of Abraxis BioScience to Celgene ($CELG) in 2010 for $2.9 billion and APP Pharmaceuticals to Germany’s Fresenius two years earlier for billions. (Abraxis developed Celgene’s anti-cancer drug Abraxane.) He’s now reportedly the richest man in Los Angeles, where he owns a piece of the NBA’s Los Angeles Lakers and has been connected with efforts to bring an NFL franchise back to the city.
SOURCE:
Bringing genomic medicine into clinical practice by placing supercomputers in the hands of physicians at point of care
WASHINGTON—-Dr. Patrick Soon-Shiong, Chairman of NantHealth and the Chan Soon-Shiong Institute for Advanced Health announced a revolutionary advance in cancer treatment that will reduce the necessary time for analysis from 8 weeks to an unprecedented 47 seconds per patient. For the first time, oncologists can compare virtually every known treatment option on the basis of genetics, risk, and cost – before treatment begins, not after.
Alongside Senator Bill Frist, MD, of the Bipartisan Policy Center and J. Michael McGinnis, MD of the Institute of Medicine and Doctors Helping Doctors, Dr. Soon-Shiong reported on the successful real-time analysis of the largest collection of tumor genomes in the United States, of 6,017 cancer genomes from 3,022 patients with 19 different cancer types, in the record time of 69 hours. Genomic analysis has taken an average of 8 to 10 weeks to complete. That delay leads not just to less efficient, more costly care, but sometimes to the wrong course of treatment altogether – and, thus, higher mortality. “Incorrect care that leads to loss of life is unacceptable,” said Dr. Soon-Shiong, “and from today onward, it will no longer be necessary.”
Oncologists currently prescribe a course of cancer treatment based on the anatomical location of the cancer. Yet a patient with breast cancer could benefit from the positive results discovered from a patient with lung cancer, if the underlying molecular pathways involving both cancers were the same. The inability to utilize genomic sequencing to guide treatment has been due to the inability to convert a patient’s DNA into actionable information in actionable time.
But by collaborating with Blue Shield of California, the Chan Soon-Shiong Institute for Advanced Health, the National LambdaRail, Doctors Helping Doctors, Verizon, Bank of America, AT&T, Intel, and Hewlett-Packard, NantHealth has built a supercomputer-based high-speed fiber network that will not only provide thousands of oncology practices with life-saving information, but do so in exponentially faster time. “Doctors will finally be able to provide higher-quality treatment in a dramatically more efficient, effective, and affordable manner,” says Dr. Soon-Shiong.
“It currently takes approximately two months and tens of thousands of dollars to perform the sequencing and analysis of a single cancer patient’s genome. We can’t reduce the cost of care and improve outcomes in cancer if we don’t have the capability to know the right treatment for the right patient before treatment begins. We needed a national supercomputing infrastructure that brings genomic medicine into clinical practice. By placing supercomputers in the hands of physicians, that need is now a reality,” said Dr. Soon-Shiong.
Accuracy will also be radically improved. Among NantHealth’s partner oncologists utilizing its fact-based software platform (eviti – http://www.eviti.com) the number of cases where doctors have made incorrect recommendations has dropped from 32% to virtually zero. “With this patient-centered, fact-based approach to collecting and analyzing data, millions more patients will have a better chance of beating cancer,” Dr. Soon-Shiong emphasized. Over the past 12 months over 2,000 oncology practices representing 8,000 oncologists and nurses have successfully installed and utilized this fact-based (eviti) software platform, positively impacting thousands of cancer patients lives.
THE RESEARCH PROCESS
In July 2012, NantWorks’ scientific team (Five3 Genomics – http://www.Five3Genomics.com) collected 6,017 tumor and germline exomes, representing 3,022 cancer patients with 19 unique cancer types. The sample collection included: 999 breast cancer; 1.156 kidney and bladder cancer; 985 gastrointestinal cancer; 744 brain cancer; 745 lung cancer; 670 ovarian, uterine and cervical caner; 436 head and neck cancer; 177 prostate cancer; 70 melanoma cancer; and 35 blood tumor samples.
This massive amount of data totaled 96,512 gigabytes and was successfully transferred and processed via our supercomputing, high-speed fiber netowrk in 69 hours. This overall transfer speed represents a stream of one sample every 17.4 seconds, and the supercomputer analysis for genetic and protein alterations between the tumor and normal sample completed every 47 seconds per patient.
Given the nation’s estimated cancer rate of 1.8 million new cases in 2012, this infrastructure now brings the capability of analyzing 5,000 patients per day.
He noted that medicine has continued to make dramatic advances, but the delivery of medicine has lagged far behind, stuck in a world where information is trapped, patterns get missed, and patients suffer. Powered by advanced supercomputing technology and wireless mobile health, the network has become one of country’s fastest genomic platforms with connectivity to over 8000 practicing oncologists and nurses. “This revolution in healthcare is long overdue – converging 21st century medical science with 21st century technology,” Dr. Soon-Shiong concluded.
Through NantHealth’s genomic analysis network, doctors can finally make cancer treatment more efficient, more effective, and more affordable for more patients. And with public and private partners equally as committed to reshaping the way doctors deliver healthcare and treat cancer, there are no limits to what this health information breakthrough might lead to for all cancer patients.
A network of major cancer centers including those at City of Hope, John Wayne Cancer Institute, and Methodist Hospital in Houston, have contributed to this collection of over 6,000 genomes, which also included the entire collection of exome samples from The Cancer Genome Atlas.
About NantWorks
The core mission of NantWorks, LLC, is to converge a wide range of technologies to accelerate scientific discoveries, enhance research and improve healthcare treatment and outcomes. Founded and led by Dr. Patrick Soon-Shiong, NantWorks is building an integrated fact-based, genomically-informed, personalized approach to the delivery of care and the development of next generation diagnostics and therapeutics. For more information, see http://www.nantworks.com.
Contacts
NantWorks, LLC
Jen Hodson
310.405.7539
jhodson@nantworks.com
SOURCE:
Research cache in works
by Emily Gersema – Jan. 28, 2012 01:29 PM
The Republic | azcentral.com
Supercomputing supports genetic, cancer research in Arizona: compare patient cases to tailor care
Having this vault of medical information is a dream for doctors, specialists and researchers who are trying to tailor medical care to the individual needs of their cancer patients. Despite huge advances in research and medicine, doctors have no one-stop shop for up-to-date clinical-trial results, other medical cases and genetic maps of their patients.
With access to this massive library, cancer doctors potentially could specify with precision the dosages of medicines, chemotherapy and radiation therapy for their patients by comparing those cases to those of other patients with similar genetic makeups and similar cancers.
In effect, this supercomputer could be a gateway to personalized medical care, as its creator, billionaire scientist Patrick Soon-Shiong, envisions it. His staff at CSS Institute for Advanced Health in California, which owns the project, and supporters of personalized medicine said the vault also could help reduce doctor error in the diagnosis and treatment of patients.
Better treatments and more accurate diagnoses could help lower the cost of medical care and enable patients to get treatment at home instead of at the hospital, they said.
The presence of the supercomputer could put Phoenix on the cutting edge of medical research and treatment. The path to these potential medical breakthroughs, however, is fraught with privacy concerns. Patient advocates fear the project could open a pathway to exploitation if patient information isn’t confidential. They want assurances that the institute would require patient consent to obtain records, the records would be kept private and the project would be under close regulatory oversight.
The engine: A supercomputer
While the word “supercomputer” evokes an image of a giant computer, the machine located in the Phoenix storage site resembles a large herd of smaller computers that have been linked to one another.
“It used to be a one big monolithic thing,” said Anoj Willy, of the CSS Institute. “But now what we’re able to do is take lots of general-purpose computers and band them to create a big, superprocessing engine.”
The CSS Institute project, which involves equipment and products from Hewlett-Packard and Intel Corp., is in its earliest stages, Willy said. The institute plans to focus data collection on genetic research and cancer.
The endeavor would create at least 50 jobs with annual salaries of about $75,000. Soon-Shiong also would invest at least $200 million in development, construction, machinery and equipment to build the electronic-data-storage facility.
The institute is in the process of signing agreements with various institutions that have been sequencing genomes — the maps of DNA strands that make up living things.
Bob Peirce, senior vice president of Soon-Shiong’s Nant Holdings in Los Angeles, said that while scientists have made strides in human genomic sequencing, the maps of these sequences are scattered at different sites around the world, depending on which institution decoded them.
Researchers have not yet decoded the whole human genome, Peirce said. They have each decoded snippets.
The lack of a complete map and a one-stop shop for the genomic information for doctors and researchers impedes their progress in personalized medical treatment, he said.
This means genomic sequences currently aren’t “relevant to the average patient or the average doctor,” Peirce said.
Creating a complete map of the human genome would require a massive, computerized data center, like the one being built by Soon-Shiong in Phoenix — to decode what scientists estimate are 3 billion pairs of DNA strands.
In addition, Soon-Shiong wants the supercomputer and its data centers, including one planned for Scottsdale, to aid in mapping the genetic makeup of individual patients’ cancerous cells.
“We need to be in a position where we can analyze the genome of the cancer and determine the genome of the host patient (to treat them),” Peirce said.
Peirce offered assurances that the data would be highly secured to guard against hackers. The data could be accessed by people who are deemed “authorized users,” he said, which could include the patients themselves who are trying to monitor their conditions and care. The institute has been working with a “chief technical officer,” who worked at the Pentagon, on securing the data centers and information they contain, Peirce said. He declined to name the officer.
The concern: Privacy
Edward Abrahams, president of the Personalized Medicine Coalition, a non-profit group in Washington, D.C., said researchers are on the cusp of creating medical care tailored to each person’s needs, and they can reach that with a supercomputer.
But they are faced with several challenges. Chief among them is patient privacy, he said.
The federal Health Insurance Portability and Accountability Act guards patient privacy, but its reach is limited. Patient information is kept private within the realm of health care — at the doctor’s office, the hospital and with the patient’s insurance company, said Bob Gellman, a privacy expert in Washington, D.C.
“An institution like this (CSS Institute) is not covered by health-privacy laws,” Gellman said. “It’s not a health-care provider. It’s not an insurer.”
Gellman said a worst-case scenario would involve a patient sharing genetic information with a company or organization, only to have it misused or exploited by another party.
“The information when it sat in the health-care system — when it sat in your doctor’s office — had all kinds of protections,” Gellman said. “But if you give the information with your consent to somebody else, then someone could just go to that third party and say, ‘Give me all your information.’ “
In that scenario, the records and data are out of the patient’s control and are unprotected.
Individuals trying to solve the health problems of their autistic children, for example, may want to participate.
“That may be a perfectly rational decision.” Gellman said. “But for people who don’t know or aren’t aware of that (institution’s) motivation … you might agree to give this information, and 20 years later, you’re in litigation with somebody or you’re applying for a job and it comes up.”
Cancer Research targets human genome breathrough with supercomputer
Platform Computing LSF integrated with genetic sequencing technology
By Antony Savvas | Published: 16:04 GMT, 09 December 11 | Computerworld UK
A new supercomputing workload management system is aiding scientific work by Cancer Research and the Cambridge Research Institute’s human genome project.
Cancer Research UK is using Platform Computing’s LSF software to improve cluster efficiency and reduce IT costs on the CRI genome research.
By integrating Platform LSF with a new advanced genetic sequencing platform, the institute has already gained greater insight into genetic cancer mutations that will lead to scientific breakthroughs in the areas of cancer diagnosis, treatment and prevention, said Cancer Research.
“Platform LSF gives us the means to produce and manage a wealth of gene sequencing data that we could only have dreamed about previously,” said Peter Maccallum, head of IT and scientific computing at Cancer Research UK in Cambridge. “This has already lead to tangible published work looking into breast cancer, and is proving its worth in helping our researchers further the understanding of how cancers progress.”
Prior to implementing Platform LSF, CRI’s 21 research groups employed separate computing resources in separate locations, which drove up server costs, reduced utilisation rates and increased server maintenance.
CRI has already saved the equivalent in man hours of one full-time employee by integrating Platform LSF, says Cancer Research. As a result, the institute plans to scale Platform LSF internally by adding more servers as compute requirements increase.
CRI is also collaborating with Platform Computing to architecturally support cross-organisation systems for HPC (high performance computing) clusters, that will enable CRI to collaborate with other research organisations in order to meet the growing demand for genomics research.
In other recent medical technology news, scientists at Cambridge University are developing a computer system that can read vast amounts of scientific literature, make rapid connections between facts and develop hypotheses. Cambridge University said most biomedical scientists cannot keep on top of reading all of the publications in their field, let alone an adjacent field. As a first step to solving the problem, Cambridge has developed its CRAB text-mining tool.
SOURCES:
[…] Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz […]
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PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.