Projects Funded in the Frames of 2019 Call of State Research Grants for Basic Research

In the frames of 2019 Call of State Research Grants for Basic Research, which is administered by the LEPL Shota Rustaveli National Science Foundation of Georgia, have been funded two joint projects with participation of the Petre Shotadze Tbilisi Medical Academy:

"Involvement of ovarian cyst mucins in the production of IgG auto-antibodies cross-reacting with tumour growth factor human chorionic gonadotropin (hCG) and its subunits"
Growing evidence supports the existence of immune-surveillance mechanisms in ovarian tumour patients, including auto-antibodies to tumour associated and tumour specific antigens, tumour growth factors. Glycoprotein hormone human chorionic gonadotropin (hCG) and its hormone-specific hCGβ have been associated with epithelial tumours such as bladder, lung, oral/facial, breast, cervical, ovarian, vaginal, prostate, renal and pancreatic carcinomas. It is believed that hCG plays a role of autocrine growth factor for tumor cells. Scientific team reported, that majority of patients, with ovarian cyst, but not those with ovarian carcinoma had significantly elevated levels of serum auto-antibodies of IgG isotype against hCG and its subunits. They further demonstrated, that these auto-antibodies predominantly belong to the IgG2 subclass and it is plausible that they cross- bind to sugar side chains of hCG and its subunits, but originally are elicited against other glycoproteins. Ovarian cyst fluids constitute one of the richest sources of blood group mucins. Scientific team proposed, that protective auto-antibodies detected in patients with ovarian cysts are cross-reacting with hCG and its subunits through their sugar chains, but are elicited against oligosaccharides of blood group mucins produced by the ovarian cysts. The project aims to check this hypothesis and to investigate whether naturally-occurring in the sera of patients with benign ovarian cysts IgG auto-antibodies to hCG and its subunits, cross-react with ovarian cyst fluid mucins.

"Discovery and understanding role of epigenetic alterations in patients with hematological malignancies residing in Country of Georgia a region affected by Chernobyl explosion"
Although global deaths caused by different types of cancer have been declining, managing this devastating disease remains challenging, particularly in our country Georgia, which is situated, approximately 1448 km from the site of the Chernobyl nuclear power plant accident, which occurred in 1986. Food products and manufactured goods were shared and distributed among those 15 republics including Georgia. All these factors contributed to the exposure of Georgians to low-dose radiation. A decade after the Chernobyl nuclear power plant accident, an increased incidence of hematological malignancies, including multiple myeloma (MM) was observed among people residing in the contaminated region. While the effects of radiation on DNA are widely studied, radiation can also damage RNA through alteration of RNA processing mechanisms. Our long-term interest includes, but is not limited to, understanding the broad effects of low-dose radiation on transcriptome changes through epigenetic mechanisms, including its effects on RNA splicing and its regulation. To achieve goals, scientific team will explore the effects of low doses of radiation on RNA splicing in GE Pts (Georgian patients with hematological malignancies multiple myeloma (MM)) for the following reasons: (1) an increased incidence of MM has been reported in the region affected by the Chernobyl accident; (2) their ongoing studies that monitor alterations in the transcriptome of patients with MM showed a significant impact of splicing alterations on the overall clinical outcome for these patients; and (3) the fundamental role of RNA splicing in human biology and its relevance in cancer are among the most unexpected and dramatic findings that have arisen from the cancer genome sequencing project. The hypothesis of this application is that Georgian MM patients (GE Pts) exposed to the Chernobyl accident may have acquired transcriptome changes through epigenetic alterations, with particular emphasis on altered RNA splicing. To test hypothesis: (1) scientific team will determine the RNA splicing signature in GE MM Pts and (2) identify the cause of altered splicing in these patients. In taking these approaches their studies will identify selective genetic alterations in GE MM Pts and will lead to the identification of novel biomarkers and drug targets, consequently providing unique therapeutic possibilities for these patients.

MoCa and IADL data correlation in individuals with mild cognitive impairment
Young Researcher:
Nino Shiukashvili
Montreal Cognitive Assessment (MoCA) test has been shown to be a reliable tool to detect mild cognitive impairment (MCI). In 2015 the indicated tool was translated in Georgian and the consequent validation was conducted (Janelidze, 2016). Besides, the randomized population study (N=1000) was conducted in order to estimate the prevalence of mild cognitive impairment (MCI) in Georgia (Nadareishvili, 2018). Based on this study, the prevalence of any MCI was 13.3% and it was widely associated with the age (>65), with the level of education, hypertension and diabetes. The main indicators are similar to studies in Europe and US. Besides, there are some studies underlying the positive correlation between Mild Cognitive Impairment (MCI) and Instrumental Activities of Daily Living (IADL) (Katrin Jekel, 2015). Based on these studies, IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits.

Projects Funded in the Frames of 2019 Call of State Research Grants for Basic Research Results