YEDITEPE UNIVERSITY BIOTECHNOLOGY SOCIETY
ABSTRACTS
PROF. DR. CLAIRE LEGAY
The molecular mechanisms of neuromuscular junction formation and the genetic associated
diseases.
The topic of my talk will be to describe the molecular mechanisms of formation of a specific synapse, the neuromuscular junction (NMJ) and the genetic diseases caused by defects in this process. My talk will be at the crossroads of neurosciences, cell biology and genetics. NMJ activity is indispensable for life since this synapse between a motor neuron and a muscle is responsible for muscle contraction. The formation of the NMJ is a complex process that occurs
in a temporal, progressive and spatial resolution. A number of organizing signals and their roles have been described in the past twenty years. However, a limited set of molecules are
really indispensable for the formation of this synapse. These factors include MuSK, LRP4, agrin, Rapsyn and Dok-7. MuSK and LRP4 form a co-receptor aggregated in the middle of the
muscle where it drives the formation of this synapse. It is a signaling hub that induces and controls different steps of synapse formation, maintenance and functioning. This co-receptor
has several ligands including the secreted glycoproteins Wnts. I will focus on the role of Wnts
in the development of this synapse and the pathology associated with mutations in the Wnts
binding domain on MuSK.
RAGHU KALLURI, M.D., PH.D.
Exploiting the Biology of Exosomes for Diagnosis and Treatment of Cancer
Humans circulate trillions of exosomes at all times. Exosomes are extracellular vesicles with a size range of 40-150 nm and a lipid bilayer membrane; and
are released by all cell types. Normal exosomes contain DNA, RNA and proteins. Some proteins such as CD9, CD63 and flotillin are often detected on the surface of exosomes and serve as markers. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags. Although their precise physiological role remains largely unknown, is it suggested that exosomes may mediate specific cell-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity and metastasis. Circulating exosomes could be used as liquid biopsies and
non-invasive biomarkers to potentially inform on early detection and diagnosis of cancer patients. Exosomes can be used for the treatment of cancer. This lecture will highlight some of the recent advances in the area of exosomes biology and their utility in the diagnosis and treatment of cancer. Additionally, the use of exosomes in personalized
therapy for cancer patients will be discussed.
ASSOC. PROF. MARIE LIPOLDOVÁ
Molecular and Cellular Immunology and Genetics of Pathogenesis of Leishmaniasis; GeneMapping, Functional Diversity, Common and Species-Specific Control
Complex diseases, in contrast to diseases caused by mutations in a single gene, are responsible for the largest part of human morbidity and mortality. These diseases are controlled
by multiple genes – QTL (quantitative trait loci) and hence their pathogenesis cannot be explained by effects of a single gene with omission of others. Leishmaniasis is a prototypical complex disease and it has served as a major paradigm of immune response to an infectious agent. It is caused by intracellular protozoan parasites of the genus Leishmania and transmitted
to vertebrates by phlebotomine sand flies. Infection can be asymptotic or led to a large spectrum of clinicopathological manifestations. The basis of these differences is not well understood, but a large part of this variation is likely genetic. We established that susceptibility to Leishmania major is multigenically controlled (1) and detected 23 Lmr QTLs (Lmr = Leishmania major
response) that regulate the response to infection by L. major (2-4).
We combined the genetic mapping of susceptibility to leishmaniasis with a detailed analysis of pathology, immunology, and parasite load of individual mice. This revealed that
surprisingly the effects of individual Lmr loci do not simply increase or reduce the expression of
immunological and pathological parameters in the direction of progression or healing, but each
locus affected change in a subset of parameters, whereby these changes did not necessarily shift
all parameters towards progression or healing, but the directional changes of individual parameters caused by the same gene could frequently point in different directions. Lmr loci were
involved in multiple gene-gene interactions (2, 3) and some of them exhibited gene-sex interactions and thus operated differently in males and females (4). We also concentrated on more precise definition of genetic and functional control of susceptibility to L. major and on finding potential links between mechanisms influencing
susceptibility to L. major and a closely related species L. tropica. Comparison of L. tropica and L. major infections indicated that the strain patterns of
response are partly species-specific, with different sex effects and largely different host susceptibility genes (5). On the basis of the observed strain differences we have performed 2
linkage analysis of the responsible genes. We have selected strain CcS-16 that is highly susceptible to both L. major (6) and L. tropica (5), but also exhibits marked differences in
systemic response to these two parasites. In F 2 hybrids between BALB/c and CcS-16 we detected
and mapped eight genes, Ltr1-8 (Leishmania tropica response 1-8) that control various manifestations of disease. Comparison of genetic control of response to L. tropica and L. major
might indicate some common and some distinct mechanisms in response to these two parasites. We compared genetic relationship between the Ltr (7) and Lmr (6, 8) loci detected in the strain CcS-16. Five loci co-localize with the previously described loci that control susceptibility to L. major, three are species-specific. Ltr2 co-localizes not only with Lmr14, but also with Ir2
influencing susceptibility to L. donovani (9) and might therefore carry a common gene controlling susceptibility to leishmaniasis (7). Current (10) and future genetic, genomic and functional studies will help to figure out mechanistic basis of the effects of Lmr and Ltr genes and to correlate them with pathology of the
disease.
C. RUTH ARCHER, PH.D.
How the evolution of aging and lifespan in either sex is shaped by selection and sexual conflict
As we grow older we become less fertile and have a higher risk of dying. These changes characterise
aging. For a long time, we thought that aging was inevitable and that even if we went to the farthest
flung corners of the galaxy, any species that we found there would show these age-associated
changes. As we study different organisms it is becoming clear that some species do escape aging, and
become more fertile and less likely to die as they grow older! Even within species that age, the
tempo and severity of these changes in fertility and mortality differ enormously. My research aims to
understand why patterns of aging are so variable both across and within species. In my talk I will
focus on sex-differences in aging to discuss how sexual selection and sexual conflict drive differences
in patterns of aging between males and females.