Projects

Next generation sequencing

Next generation sequencing (NGS) technologies enable rapid generation of data by sequencing massive amounts of DNA in parallel using diverse methodologies. Using the immense potential of NGS, enormous effort has made strides to apply these instruments to very diverse biological problems, among them, large-scale genetic surveys of human populations at quantum resolution—the single nucleotide. Genome sequencing and RNA-Seq are the two most popular current applications of NGS. Here at the University of Debrecen Genomics Center, the Illumina HiScanSQ NGS platform focuses more on specific applications like monitoring complex mixtures of polynucleotide species in a population of organisms called metagenomics. Also, very importantly, we are developing targeted library re-sequencing of recombinant clones, characterization of transcription factor binding sites (chromosome immunoprecipitation, ChIP), assessment of the methylation status of cytosine residues, a marker of epigenetic modification as part of our epigetnetic platform. Another specific science driven application is our unbias discovery effort of germline and somatic mutations by exome capture technologies. We can expect NGS to find wider use in research and in the clinic through genome sequencing for cancer patients, facilitating medical diagnosis in the near future. Our goal is to develop a sustainable NGS platform that will allow us to enter the era of personalized medicine.

 


Affymetrix

Chronic inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and autoimmune disorders e.g. rheumatoid arthritis (RA), and inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis have showed increasing incidence in the Hungarian population in the past 10-15 years. These are multifactorial diseases; several inflammatory cells and agents are involved in the development of these diseases and the genetic background is also an important factor.

Our aim is to identify gene expression patterns of peripheral blood of diseased patients and healthy controls using Affymetrix microarray technology and Real-Time Quantitative PCR. We think that identification of disease specific gene expression signatures could help the better diagnosis of the diseases or predict the efficacy or responsiveness of the patients to different therapies.


Epigenetics

I entered in reaseach in the year when the sequence of the Human Genome was published. Today sequencing it is not a challenge any more. The advance in technology openned up the doors of functional genomics. Studiing the modified genome, the expressed genome or the protein-DNA interaction revels us layers of regulation. My research interest is mainly in building bridges between what we can study and what we should study for the benefits of patients. For this in the last period we developped and thoroughly tested an assay design system for detecting small regulatory RNA molecules, we developped controlls for Chromatin immunoprecipitation studies and new protocolls for ChIP. We plan to develop technologies that would allow the transition of functional genomic studies from basic science to clinical research.

Epigenetics in broad sense is studying the molecular details occuring on DNA without a change in the nucleotide sequence and the posttranslational modifications on the histone tails that together are able to determine which genomic regions will be active in a specific cell type. These modifications are part of gene expression regulation and cell fate determination. In a more specific approach epigenetics deals with the mechanisms responsible for the inheritance of traits determined by environmental factors.

Most important physical carriers of epigenetic memory are mehtylated and other modified nucleotides, posttranslational modifications of histone tails and small regulatory RNA-s.

Currently used methods that enable the study of epigenetic changes are under development and standardisation. The goal is to create reliable methods that will allow us to enter into clinical research.


Biobanking

Small cell lung cancer (SCLC) is almost always diagnosed as a late-stage disease with metastases, having to resort to chemotherapy or radiotherapy instead of surgery. However, even with combined chemo/radiotherapy, the 5-year survival rate for SCLC is only about 5%. Two areas of SCLC biology is of paramount importance to improve treatment: we need to understand why SCLC cells form metastases at such a high success rate, and we also need to explore the basis of tumor regrowth after chemo/radiotherapies. Our major research interest is to understand the role of aberrantly expressed microRNAs in SCLC, specifically in the metastatic process. In our previous work we combined microarray and qRT-PCR analyses to identify microRNAs aberrantly expressed in small cell lung cancer. Our further work demonstrated that miR-126 overexpression has a negative effect on SCLC cell proliferation, partly through targeting SLC7A5.


Protein and cell engineering

The Laboratory of Protein Expression and Cell Engineering operates as a research and development lab as well as a core facility within the Center for Clinical Genomics and Personalised Medicine. As a development laboratory, we are working on proprietary technologies and biotech products in the field of protein expression, monoclonal antibodies, recombinant proteins, cell engineering, functional genomics and epigenetics. As a core facility, we provide advanced protein expression services using optimised synthetic genes and a wide range of host organisms (bacterial, yeast, insect, mammalian) for small and large scale protein production, and equipped for state-of –the-art protein purification and biochemical/biological characterisation – a full Gene-to-Protein service.

Also, we are routinely developing single and multiple transgenic or knockout stable mammalian cell lines using cell/genome engineering technologies for research, bioassay, recombinant protein production, or any custom applications to your needs. The laboratory is also offering custom monoclonal antibody development starting from antigen sequence, through epitope design up to small or large scale purified antibody preparations. We have a custom recombinant cytokine development workflow and offer cytokine expressing stable cell lines or purified cytokines. We are ready to help you with our consultation services for project and method development and special services in the field of protein engineering, directed molecular evolution, phage display technology and high throughput screening. Our services are fast and quality controlled internally with the potential for external QA in the near future.

The Laboratory Establishment Project was sponsored by MAG Zrt. - Hungarian Economic Development Center, North-Great Plain Region Gábor Baross Program, REG_EA_KFI_09-INNANTet.

 

Please, visit the laboratories website at http://www.proxencell.com.

 


Personalized medicine through genomics

The future of medicine will clearly be centered around personalized care and clinical genomics meaning that every individual will receive prevention tips, diagnosis and therapy based on the combination of their own genomic background and lifestyle. In clinical genomics, instead of single gene differences, only gene panels could solve unmet needs in the clinical settings by determining early diagnosis, disease progression, subtypes; or whether a patient would respond to a specific therapy before even starting it by analyzing the gene expression patterns of the least invasively obtained peripheral blood samples or tissue biopsies. These could give insights into the pathogenesis of autoimmune conditions, identify new targets for future therapies of predict response to treatments available now therefore reducing healthcare routes and costs.