Cellular stress

Cellular stress

Laboratory of Genome Integrity

Senior research group

Cellular stress pathways are essential for cancer cells' survival and significantly contribute to therapeutic resistance. They help the cells to deal with various cancer hallmarks, including elevated DNA damage accompanied by accumulation of mutations, DNA replication problems, accumulation of defective proteins, free radicals, nutrient deficiency, hypoxia, etc. Our methods and expertise identify and target these stress pathways directly inside cancer cells. Such research has great potential in finding new prediction markers, improving standard anticancer therapy, and suggesting new therapeutic targets.

Research interests

DNA damage and repair and genomic instability
Replication stress
Proteotoxic stress and proteostasis
Mechanical stress
Oncogenic and free radicals stress

Current projects

Exploration of mechanical stress-promoted perturbation of the cell cycle in cancer cells.
Identification and structural characterization of novel NPL4 inhibitors and insight into its mode of action.
Cannabidiol as a potential attenuator of the efficacy of chemotherapeutics.
Development of nano-formulated diethyldithiocarbamate-copper complex as an anticancer drug.
Identification of new compounds with senolytic effect and mechanism of their action in senescent cells.
Insight into cellular proteotoxic stress response using new microthermal protein damage methodology.
Effects of long-term mild hypothermia (fever-like hyperthermia) on cancer cells.
Cellular DNA damage response in the context of cance.

Patents

METHOD OF PRODUCTION OF SYNCHRONIZED ADHERENTLY GROWING CELL LINES AND DEVICE FOR CARRYING OUT SAID METHOD (Mistrík)

Patent: CZ 302682; Granted: 20.7.2011; Ownership: Palacky University Olomouc; Inventors: Mistrík Martin, Bártek Jiří
Published Application PCT/CZ2010/000043 under WO 2010/118709 (21.10.2010)
Patent: EP 2419503; Granted: 19.12.2012; Ownership: Palacky University Olomouc; Inventors: Mistrík Martin, Bártek Jiří

Status: Terminated

DEVICE FOR PRODUCTION OF SYNCHRONIZED ADHERENTLY GROWING CELL LINES (Mistrík)

Utility Model: CZ 19628; Granted: 11.5.2009; Ownership: Palacky University Olomouc; Inventors: Mistrík Martin, Bártek Jiří

Status: Terminated

Open positions

Project:	Cellular stress in health and disease
Supervisors:	Mistrík Martin Ph.D., Moudrý Pavel Ph.D., Škrott Zdeněk Ph.D.
Available:	3
Intended for:	Doctoral training

Project:	DNA damage signaling in the cellular response to stress
Supervisors:	Mistrík Martin Ph.D.
Available:	1
Intended for:	Doctoral training
Summary:	1 place in full-time study

Project:	DNA damage signaling in the cellular response to stress
Supervisors:	Mistrík Martin Ph.D.
Available:	1
Intended for:	Doctoral training
Summary:	1 place in full-time study

Project:	Study of DNA double-strand break repair in tumor model
Supervisors:	Mistrík Martin Ph.D.
Available:	1
Intended for:	Doctoral training
Summary:	The so-called double-strand breaks (DSB) are the most lethal DNA lesions, which can be potent sources of mutations and thus become the beginning of irreversible genetic changes leading to degenerative illnesses, including cancer. At the same induction of DSBs introduced in the proper setup can become an unsolvable problem for the cells, particularly in specific genetic backgrounds typical for cancer, which fact is the rationale for a plethora of cancer treatment strategies. Thus the way cells deal with DSBs is under the great interest of current medicinal and biological research. The Ph.D. student will practice several methods of induction of DSBs via various sources such as gamma rays, alpha particles, UV light and various chemical inducers. Next will be studied the molecular mechanisms the cell deal with this type of DNA damage. Emphasis will be put on differences between normal and cancer cells and their potential exploration for cancer therapy. Student will also learn mutiple laboratory techniques including cell culture, RNA/DNA transfections, advanced microscopic techniques, live-cell imaging, and various biochemical analysis of proteins.

Project:	Signaling DNA damage in cellular response to stress
Supervisors:	Mistrík Martin Ph.D.
Available:	1
Intended for:	Doctoral training
Summary:	Our DNA is constantly under threat from DNA damaging agents. If unrepaired DNA damage can lead to errors during genome duplication, including the mutations that can lead to cancer, contribute to aging and other human diseases. Cells have evolved elaborate repair mechanisms to fix this damage and ensure that the genetic information is faithfully reproduced, and we would like to understand these repair mechanisms at the molecular level. We ultimately aim for a complete molecular and cellular understanding of critical DNA repair pathways that act on DNA damage. The Ph.D. student will practice several molecular and cellular techniques, including cell culture, RNA interference, immunofluorescence microscopy, live-cell imaging and immunoprecipitation of proteins. He/she will also learn novel and powerful techniques, such as super-resolution microscopy and purification of proteins on newly synthesized DNA.