Biochemie

Školitel: doc. RNDr. Jaroslav Turánek, DSc.

OBJECTIVES: The research aims the field of nanomedicine, especially to immunopharmacotherapy of cancer, infection diseases (vaccines) and diagnostics. Outcomes (publications and eventually patent applications) will contribute to development of modern immunotherapeutics like vaccines and adjuvants, targeted anticancer/antiviral drugs and theranostics for in vivo imaging and monitoring the progress of treatment.

FOCUS: Doctoral research projects focus on preparation and complex characterisation of biocompatible functionalised nanoparticles applicable for development of modern therapeutics and theranostics. Student will benefit from world class infrastructure at VRI, including laboratory of physical-chemical methods (microfluidic system, MALS, MADLS, NTA, TRPS, UV VIS/CD/FL/FT-IR spectroscopy, Field Flow Fractionation, thermal methods like DSC and ITC, laboratory of microscopic methods (AFM, TEM, SEM and confocal microscopy), laboratory of tissue culture and biotechnology (FPLC/HPLC, various unique bioreactors for production of recombinant proteins, ultracentrifugation, QRT-PCR, multifunctional multiplate reader, flow cytometry and cell sorter), laboratory of surgery and in vivo imaging (microcomputer tomography microCT and optical whole body scanner) and animal house for experiments on small and large animals, laboratory of histology.

EXAMPLES of potential doctoral projects:

• Preparation and formulation of mRNA in liposomes and evaluation of transfection potential in vitro and in vivo, study of immune response in vivo on mice model
• Expression, purification and characterisation of recombinant proteins/antigens (e.g. HIV-1, influenza, Borrelia), construction of experimental vaccines and study of immune response in vivo
• Preparation of nanoparticle based contrast agents (e.g. gold nanoparticles) for in vivo imaging via microCT and MRI: tumour and thrombi as targets
• New antiviral drugs and their formulation, modification for targeting of macrophages, testing in tissue culture and in vivo models
• New molecular adjuvants and immunomodulators: formulation in nanoliposomes, testing in models in vitro and in vivo
• Nano and microstructures for non-invasive vaccination: preparation, characterisation and testing in in vivo models with model antigens, evaluation of immune response (mice, pig)
• Physiologically active compounds from venom, characterisation, purification, preparation of antisera

MORE INFORMATION: www.vri.cz/en//

PLEASE NOTE: before initiating the formal application process to doctoral studies, all interested candidates are required to contact Ass. Prof. RNDr. Jaroslav Turánek, Res. Prof. (turanek@vri.cz) for informal interview.

Školitel: Mgr. Jan Víteček, Ph.D.

BACKGROUND: Cardiovascular diseases currently contribute the biggest burden of the mortality worldwide. The molecular mechanisms behind are frequently underexplored.
Current pre-clinical research of cardiovascular diseases utilizes animal models predominantly. However, they provide low throughput and may fail to recapitulate certain aspects of human pathophysiology. That is why an in vitro model can be a suitable alternative especially if combined with biological material of human origin. OBJECTIVES: Provide insights into selected aspects of a cardiovascular disease using a specifically tailored vasculature model.
FOCUS: The group of Jan Víteček is focused on thrombolysis in connection with ischemic stroke treatment and the role of blood flow in vascular pathophysiology.
EXAMPLES of potential student doctoral projects:
Mechanisms of thrombolysis and recanalization; Biochemical mechanisms of clot thrombolytic resistance; Role of blood flow in development of aneurysms and stenoses; Electrical phenomena in vasculature homeostasis.
METHODS: Vascular model construction, cell cultures, mechanobiological characterisation of blood clots, fluorescence confocal and electron microscopy, basic approaches of biochemistry and molecular biology.
MORE INFORMATION:
https://www.ibp.cz/en/research/departments/biophysics-of-immune-systems/research-profile/group-of-vitecek-jan
https://www.strokebrno.com/members/institute-of-biophysics/
PLEASE NOTE: Before initiating the formal application process to doctoral studies, the candidate is required to contact Jan Víteček for an informal discussion.

Školitel: doc. Mgr. Pavel Bouchal, Ph.D.

OBJECTIVE: Renal cell carcinoma (RCC) represents a serious oncological disease with the highest incidence in the Czech Republic. The reliable molecular markers related to the critical clinical scenarios are still missing.

FOCUS: We will use a novel mass spectrometry technique in data independent acquisition mode to acquire digital fingerprints or a well-characterized set of RCC tumors collected accross the Czech Republic. We will aim to identify protein markers or patterns relevant for the clinical scenarios in question, characterize these markers functionally, modulate them therapeutically, and validate.

EXAMPLE of potential doctoral project - the student will focus on:
*Protein biomarkers and patterns identifying patients with localized RCC with a high risk of relapse
*Protein biomarkers and patterns identifying patients with metastatic RCC with a high risk of poor response to available therapy
*Functional characterization of identified proteins using CRISPR/Cas9 technique followed by analysis of cell migration, invasiveness and sensitivity to potential inhibitors.
*Development of a targeted mass spectrometry method for a routine quantification of the novel marker proteins.
We expect that the identified potential biomarkers, therapy targets or molecular patterns will contribute to a more efficient treatment of RCC patients. Supported by Ministry of Health of the Czech Republic, project NV19-08-00250.

MORE INFORMATION: http://www1.sci.muni.cz/en/UBCH/Proteomika

PLEASE NOTE: Before initiating the formal application process to doctoral studies, the candidate is required to contact Doc. Pavel Bouchal for informal discussion.

Školitel: prof. RNDr. Omar Šerý, Ph.D.

Alzheimerova choroba vzniká jako důsledek více faktorů, mezi které patří faktory životního stylu, ale také genetické faktory. Mírná kognitivní porucha (MKP) je heterogenní klinická jednotka, u které se rozeznávají dvě formy, a to amnestická forma mírné kognitivní poruchy, kdy dochází k objektivní poruše paměti a neamnestická forma mírné kognitivní poruchy. Amnestická forma MKP je charakterizována poruchou paměti, případně postižením dalších kognitivních funkcí, které však nedosahují úrovně demence. Udává se, že tato forma přechází do Alzheimerovy choroby ve 12-18% za rok.
V rámci disertační práce budou sledováni a vyšetřováni pacienti s Alzheimerovou chorobou a s amnestickou formou MKP s cílem zjistit, zda některé genetické markery, které souvisejí s Alzheimerovou chorobou, nejsou přítomny u MKP, což by mohlo v budoucnu přispět k časnému záchytu rizikových osob. Doktorand bude v rámci své práce izolovat DNA ze vzorků pacientů. Pro genotypizace minimálně 400 probandů bude použita metoda NGS sekvenování a kapilárního sekvenování. Jedním z cílů disertační práce bude také porovnávání vlastností buněčných kultur získaných z fibroblastů pacientů s Alzheimerovou chorobou. Zkoumány budou např. rozdíly transkriptomu. Výsledná data budou statisticky analyzována a budou začleněna do stávajícího modelu patogeneze Alzheimerovy choroby.

Školitel: prof. RNDr. Jana Kašpárková, Ph.D.

OBJECTIVES: With the intention to better understand the effects, which may play an important role in the biological (pharmacological) action of new combinations of anticancer metallodrugs and agents capable of targeting mechanisms connected with resistance of tumor cells to metallodrugs, new, “dual or multi-action” combinations of chemotherapeutics having the genes that confer resistance to anticancer drugs (cancer resistome) as one of the targets of their action will be introduced and tested. New combinations of metallodrugs and molecules targeting cancer resistomes capable of dual targeting of resistance mechanisms and at the same time DNA will be developed; detailed studies of cytotoxicity, selective targeting into tumor cells, inactivation by coordination to sulfur-containing proteins, DNA binding, cell accumulation, efficiency to affect DNA repair, tolerance of the resulting DNA damage, cellular responses and signaling pathways of new combinations will be performed. To achieve these goals, modern methods of biochemistry, molecular biophysics, oncology, and cell pharmacology will be used.

FOCUS: The aim of this research is to address the need for new combinations of chemotherapeutics capable of targeting mechanisms connected with the resistance of tumor cells to anticancer drugs. The identification of such combinations will improve the efficiency of drugs to kill tumor cells. These studies will be performed using modern biochemical methods and methods of molecular and cellular biophysics available at the Department of Molecular Biophysics and Pharmacology of the Institute of Biophysics, Czech Academy of Sciences in Brno.

EXAMPLES of potential student doctoral projects:

• Targeting resistance to chemotherapy of tumor cells to reinstate their susceptibility to novel, existing and unsuccessful anticancer metallodrugs
• Nanocarriers co-encapsulating two or multiple therapeutic agents
• Synergistic effects of polypharmacology involving metallodrugs in combination with other drugs capable of targeting cancer resistome

MORE INFORMATION: https://www.ibp.cz/en/research/departments/molecular-biophysics-and-pharmacology/info-about-the-department