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The Warsaw Voice » Special Sections » September 30, 2013
Neurobiology
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Unlocking the Secrets of the Genome
September 30, 2013   
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A group of Warsaw researchers have set out to sequence 150 human genomes in order to gain a better insight into chemical and biological processes that promote the development of cancer cells as well as diseases such as schizophrenia.

The genome is the complete set of human genetic information stored in the form of DNA sequences. The information encoded in our genome determines everything from our eye color to whether we are likely to die of cancer. The researchers, from the Polish Academy of Sciences’ Nencki Institute of Experimental Biology in Warsaw, are focusing on cell pathology, especially brain tumor transformation.

The Nencki Institute’s Laboratory of Molecular Neurobiology is studying genomes to decipher the information they carry about human brain cells. While most researchers worldwide focus on studying the functions of one or several genes, the problem is that each human cell consists of over 20,000 genes and to understand the functioning of the whole cell in a specific tissue, it is necessary to find out how the entire genome works in a particular setting, the Nencki Institute researchers say.

Different genes are active in different types of cells. Even though each cell has an identical set of genes, these occupy no more than a few percent of the human DNA. Around 80 percent of the DNA contains sequences regulating the expression of genes, Nencki Institute researchers say. It also turns out, they add, that a set of regulatory sequences differs in cells of different types and under various conditions. Therefore without knowing how the whole genome is read out in a given type of cell, it is impossible to understand its functioning, the researchers say.

“Our lab focuses on large-scale genome research as we try to analyze at the same time the level of regulation for all genes present in the genome,” says Prof. Bożena Kamińska, head of the Laboratory of Molecular Neurobiology at the Nencki Institute. In the next five years the lab plans to sequence 150 human genomes to get a better understanding of cell pathology, especially brain tumor transformation.

Tumors are caused by gene mutations, but so-called epigenetic effects, resulting from reversible modifications of protein-DNA complexes inside the tumor cell and in its vicinity, are also important. These changes can influence the reading of genetic information.

Most previous strategies for fighting tumors were based on attempts to inhibit the functions of molecules encoded by the altered genes and find ways to kill the tumor cells or stop their proliferation. This is a difficult task, because many tumor mutations increase life span and prevent cell death. As opposed to gene mutations, which are irreversible and impossible to correct, epigenetic changes can be reversed. A new approach has therefore surfaced in fighting tumors, focused on investigating epigenetic mechanisms both inside the tumor and in its microenvironment.

“We want to understand the chemical and biological processes which occur within tumor vicinity and facilitate tumor progression,” says Kamińska. “Why? A tumor cell shapes its microenvironment to support its growth, actively inhibiting the immune system. Instead of attacking the tumor cell directly, we can try to restore the original features to its environment, which could limit the development of the tumor or even eliminate it.”

The research at the Laboratory of Molecular Neurobiology focuses on deciphering the whole genome information not only in laboratory cell lines, but also in cells from human brain tumors. This is possible due to collaboration with the Institute of Psychiatry and Neurology and the Children’s Memorial Health Institute in Warsaw, which supply samples of tumors removed from patients for research. From those tumors, different types of cells are isolated, including glioma initiating cells, which are important for tumor recurrence.

“The obvious application area for our research is medicine, especially with respect to investigating the mechanisms of brain tumor pathology,” Kamińska says. But epigenetic changes and dysfunctions in reading genetic information can also cause disorders accompanying mental illness such as schizophrenia.”

In collaboration with psychologist Prof. Janusz Rybakowski from Poznań and bioinformatics expert Prof. Jan Komorowski from Uppsala University in Sweden, the Nencki Institute researchers want to create brain-specific “maps of regulatory areas” to search them for genetic changes associated with schizophrenia.

The Laboratory of Molecular Neurobiology at the Nencki Institute has cutting-edge research equipment at its disposal. This includes devices for investigating the expression of one to several genes as well as a microarray scanner that makes it possible to investigate the expression of virtually every human gene at the same time. Another valuable purchase is a device for laser microdissection. It enables researchers to precisely cut out tissue fragments of interest or even individual cells from the tissue. The equipment installed in the lab is highly accurate: no more than 150 cells are needed to isolate ribonucleic acid (RNA) and investigate the expression profile of all genes. Together with the DNA, the RNA comprises the nucleic acids, which, along with proteins, constitute the three major macromolecules essential for all known forms of life. RNA molecules play a key role in transcribing genetic information, in the formation of proteins and in all cellular processes.

The research being conducted at the Nencki Institute also involves specialized information technology support provided by a team of IT experts, who not only process the data gathered but also create their own algorithms for analysis, which help predict, for example, the effect of a drug on individual cells. Since the information recorded about individual genomes or a full description of cell reactions may occupy half a terabyte, work is under way to equip the lab with a large server to process huge amounts of data.

O.M.


FACTFILE

The Laboratory of Molecular Neurobiology at the Nencki Institute is one of five new core facilities established as part of the Center for Preclinical Research and Technology (CePT), which is being built in Warsaw in what marks the largest biomedical and biotechnology project in Central and Eastern Europe to date.

The center is being created by a consortium of 10 research centers. The aim is to conduct interdisciplinary fundamental research and to carry out research—in areas such as structural and functional analysis, physics, chemistry, nanotechnology, biomaterials, molecular biotechnology, pathophysiology, oncology, genomics, and neurobiology—with a view to developing new methods to diagnose and treat various circulatory and nervous system diseases as well as cancer and age-related diseases.

The project’s budget is almost zl.390 million, of which 85 percent comes from the European Fund for Regional Development. The project is being coordinated by the Medical University of Warsaw, in partnership with two universities—the University of Warsaw and the Warsaw University of Technology—and seven research institutes of the Polish Academy of Sciences: the Nencki Institute of Experimental Biology; the Institute of Biochemistry and Biophysics; the Mossakowski Medical Research Center; the International Institute of Molecular and Cell Biology; the Institute of Fundamental Technological Research; the Institute of High Pressure Physics; and the Institute of Biocybernetics and Biomedical Engineering.

The Nencki Institute of Experimental Biology is part of the Polish Academy of Sciences. Established in 1918, it is the largest non-university center for biological research in Poland. Priority research fields for the institute include neurobiology, neurophysiology, cellular biology and biochemistry and molecular biology.
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