Head of the laboratory: Mgr. Lenka Gahurová, Ph.D. (née Veselovská)

Mammalian oocytes (=female eggs) are established during female embryonic development as a finite pool. They are essential for propagation of the species yet are among the oldest cells in the body – they can be several decades old in long-lived species such as humans. They preserve their quality for extraordinarily long time compared to most other cell types in the body, nevertheless, female fertility is one of the first physiological functions undergoing age-associated decline. This decline is generally associated with decreased quantity and quality of oocytes, affecting the ability to sustain successful embryonic development.
Studies on female fertility and oocyte biology are mostly performed on mouse, a classical mammalian model. However, mice are fertile only for <12 months, and cannot therefore fully recapitulate biological processes in long-lived species that are fertile for several decades. Moreover, increasing number of studies show that mechanism uncovered in mouse do not universally apply across mammals.

What we ask:
(1) What are the molecular mechanisms conferring long-term oocyte quality and what can go wrong? How is oocyte quality and quantity affected by their ovarian niche and physiological processing taking place in the ovary (such as ovulations)?
(2) How does the dynamic relationship between host and transposons affect oocyte biology, maternal to zygotic transition, and embryonic development, and does it change during maternal aging?

What we do:
We employ various sequencing (genomics, transcriptomics, epigenomics) and imaging approaches to study oocytes, ovaries and embryos of multiple short-lived and long-lived rodent species from different phylogenetic groups – especially naked mole-rat, giant mole-rat, guinea pig, coruro, blind mole rat and mouse.

Mgr. Michaela Fencková, Ph.D.

head of the Laboratory of Neurogenetics

Faculty of Science, University of South Bohemia
Branišovská 31, 37005 České Budějovice
building B, ground floor, door number 194b
 
Email: fenckm00@prf.jcu.cz
Tel. +420 387772227

Head of the laboratory: Mgr. Michaela Fencková, Ph.D.

Lucie Hrádková (technical assistant, lab manager)
Tereza Koníková (technical assistant, researcher)

Pavla Nedbalová (postdoc)

Petra Havlíčková (PhD student)
Anna Koutská (PhD student)

Alžběta Hejlková (MSc student)
Lukáš Martínek (MSc student)
Matyáš Suchý (MSc student)

Aneta Medková (BSc student)
Sera Gruber (BSc student)

MASTER STUDENT WANTED
NEW MASTER PROJECT FOR 2024/2025 

WHAT WE DO

We study genes that are important for cognitive function and investigate how can single genetic defects result in dramatic and severe neurodevelopmental disorders, such as intellectual disability (ID) or autism (autism spectrum disorder, ASD).

HOW WE DO IT

We introduce equivalent mutations that are found in individuals with ID or ASD into the genes of a fruit fly, Drosophila. We use various approaches, depending on the type of mutation, such as RNA interference (to mimic loss-of-function), overexpression (to mimic gain-of-function), or CRISPR/Cas9-based genome editing (to model missense and patient-specific variants).

The fruit fly genetic models are inspected for cognitive phenotypes. We mostly focus on habituation, a conserved form of learning that we found to be relevant for ID and ASD. During habituation, a reaction to repeated irrelevant stimuli gradually wanes. They are filtered out and our brain can focus on important matters. A typical example is learning to ignore the sound of a ticking clock. Habituation protects our brain from information overload and it is required for higher cognitive functions, such as memory. It can be assessed in both ID/ASD individuals and their Drosophila models, which makes it suitable for the investigation of disease mechanisms and treatment targets.

You can read more about genetics, molecular control and clinical relevance of habituation learning in our review.

Just as the human brain gets used = habituates to clock ticking, fruit flies can suppress their jump response to a repetition of a light-off stimulus. In the beginning, they perceive it as a danger and respond with a jump. After few repetitions, they learn that it does not cause any harm and stop jumping. Flies with habituation deficit are not able to suppress the response and continue jumping, like in the video below. Our habituation assay is thus called light-off jump habituation. With this assay, we can test 24 flies in less than 30 minutes.

We employ cell- and time-specific tools (Gal4 and split-Gal4, TARGET) to determine neuronal substrates and the developmental origin of gene-specific habituation deficit and genetic interactions to identify dysfunctional pathways and treatment targets. We also look at synapse biology as habituation is related to synaptic function (see example here). To determine the effect of habituation defective missense or patient-specific variants, we use structural modeling and molecular assays. Finally, we attempt to correct the deficits with mechanism-specific drugs.

WHY IS IT IMPORTANT

ID and ASD are major and co-occurring neurodevelopmental disorders. They represent a significant burden for the affected individuals, their families, and health care costs. The underlying mechanisms are not completely understood and there is no treatment to ameliorate the cognitive deficits. ID/ASD have mostly monogenic causes - they are caused by mutations in single genes. To date, we know >1500 such genes. They represent a window into biological pathways and treatment targets but it would take way too long if they are studied in low-throughput models, such as laboratory mice. A high-throughput model is needed. Drosophila is a great opportunity because it has high genetic conservation (75% of disease genes can also be found in fruit flies), high-throughput compatibility, and efficient tools to generate mutations and dissect the molecular mechanisms. With high-throughput light-off jump habituation, we can assess what matters the most - cognitive function. Established human habituation protocols will facilitate the translation of this knowledge to treatment trials.

What are the options for mobility within the Erasmus+ program?

Students can go on a study stay or work internship. Employees can use the Erasmus+ program for a teaching stay at a partner university or for training (educational event, shadowing, cooperation, language stay, etc.)—attention, NOT a conference.

For how long can I use the Erasmus+ program?

Study stays are usually on the length of semesters at the receiving university (1-2 semesters). The minimum duration for a traineeship is 2 months. PhD students can also use a short-term internship for 5-30 days.

Employees usually use a week (5 days plus travel), and the minimum length of stay is 2 days.

Where can I go?

With the Erasmus+ program, you can go to EU countries. A bilateral agreement must be concluded between the institutions for the type of study stay (students) and teaching stay (employees). These are EU member states: Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Finland, France, Germany, Ireland, Italy, Cyprus, Lithuania, Latvia, Luxembourg, Hungary, Malta, Netherlands, Poland, Portugal, Romania, Greece, Slovakia, Slovenia, Spain, Sweden. Then the countries of the European Economic Area (Norway, Iceland and Liechtenstein) as well as Turkey and Macedonia.

What is the amount of the scholarship for a study stay/work placement?

You can find the amount of scholarships for a specific type here:

The scholarship in the Erasmus+ program is a contribution to your stay abroad. It does not compensate for all costs.

I am interested in being in contact with international students here at the Faculty of Science/university. What can I do?

Contact the "international student club" ESN USB Budweis (https://esnusb.cz/).

Where can I get information on foreign mobility?

You can find information about foreign mobilities in the Foreign Mobilities section or on the website of the University of South Bohemia in České Budějovice.

If you do not find the information you seek, do not hesitate to contact our foreign relations department.