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Topic Abstracts

Assoc. Prof. Dr. Pedro Morouco

"Four-dimensional bioprinting: stimuli-responsive mechanisms for biomedical applications"


Three-dimensional (3D) bioprinting emerged has a highly versatile technology able to produce customised structures. The ability to produce those structures in a layer-by- layer fashion allowed a precise control over geometry, morphology and pore interconnectivity. However, those 3D structures may not be the most suitable approach for the clinical requirements. Indeed, four-dimensional (4D) bioprinting seems to promise a technology with the ability to induce planned changes at the structures, bridging the gap
between the laboratorial constructs and the native human tissues. In summary, 4D bioprinting main goal is to develop biological 3D structures, which are suitable to change their properties (e.g. stiffness, shape, volume) when triggered by a pre-defined stimulus (e.g. electricity, ionic force, light, magnetic field, pH and temperature). If on one hand it is important to develop and design new materials and processes, making those materials biocompatible is also crucial. The audience will be dared to think further on the applications of this technology. How will the stimulus be provided? By who? And on which conditions, are some of the topics which will be addressed.

Assis. Prof. Dr. Allen Liu​,

"Microfluidics for single cell mechanobiology"

The proper responses of cells to mechanical stimuli are important in numerous physiological processes. With the development of microsystem engineering tools, controlled and repeatable application of active mechanical input to single cells is becoming more available. Several microfluidic platforms have been developed for mechanotransduction research over the last decade that many focus applying a single mechanical perturbation and often to a population of cells. Here we develop a multilayer polydimethoxysilane (PDMS)-based microfluidic device with the goal of applying controlled aspiration and compression to single cells. Two independent pneumatically controlled channels above the flow channel serve to facilitate cell loading and compression when they are actuated. As a model system of cell and to demonstrate the salient features of our device, we generated water-oil- water double emulsion droplets and demonstrated trapping, aspiration, and compression of double emulsion droplets.
More recently, we have combined this with microcontact printing to confine the size of single cells and investigate the effect of static vs. cyclic compressive stress to single cells. Our unique and versatile microfluidic compression device will provide tremendous
opportunities for future single cell mechanotransduction studies. 

Assis. Prof. Dr. Gerhard Wingender,

"The role and therapeutic potential of invariant Natural Killer T (iNKT) cells in health and disease"

The immune system is commonly divided in innate and adaptive immune system. The innate immune system (a) is composed of elements that are expressed in all individuals in basically an identical form; (b) responds immediately within minutes or hours; and (c) recognizes brought patterns of molecules that are e.g. expressed by various pathogens. In contrast, the adaptive immune system, consisting of B and T cells, (a) is unique in every individual; (b) is highly specific for unique structures; and (c) has the ability to remember (memory); however, (d) it is slow to respond and requiring days for full activation. The majority of T cells, also called conventional T cells, recognize protein fragments (peptides) that are presented to them by MHC molecules.


Besides these conventional T cells, a distinct, but smaller population of T cells called invariant Natural Killer T (iNKT) cells have been describe. iNKT cells bridge the two branches of the immune system, as they share features with innate NK cells and T cells. Several unique characteristics distinguish iNKT cells from conventional T cells: (1) Their T cell receptor (TCR) does not recognize
protein fragments on MHC molecules, but rather glycolipids on the non-polymorphic CD1d molecule. (2) They do not require a lengthy differentiation phase after activation, but rather develop already as fully functional effector cells.


In line with their effector/memory phenotype, iNKT cells rapidly produce copious amounts of cytokines following stimulation, and often present the first response to infections. Thereby, iNKT cells can have a pronounced effect on the immune system, impacting a dazzling variety of different immune reactions, ranging from responses to pathogens and tumors, to autoimmune responses.
Here, I will introduce the role iNKT cells can play in various diseases and will give an overview over approaches to target them for immunotherapy.

Assis. Prof. Dr.  Shirin Tarbiat,

"PPARs, Obesity and Cardiovascular Diseases"

Peroxisome proliferator-activated receptor (PPAR) belongs to nuclear receptor super family of transcription factors, and consists of 3 isoforms (i.e., PPARα, PPARβ [also known as δ], and PPARγ). PPARα is predominantly expressed in tissues with a high oxidative capacity such as the heart and liver, PPARγ is highly expressed in adipose tissue, and the expression of PPARβ/δ is more ubiquitous. The PPARs can be activated by an array of natural endogenous ligands.Synthetic ligands have been designed for the PPAR isoforms with the purpose of therapeutic application. On ligand-binding, PPARs transactivate gene expression by heterodimerization with another member of the nuclear receptor super family, the retinoic X receptor, and this complex binds to a direct repeat sequence designated as PPAR-responsive element.


PPARα reduces hepatic fat accumulation by inducing mitochondrial, peroxisomal, and microsomal fatty acid oxidation. In addition, PPARα reduce inflammatory reactions in the arterial wall via suppression of several proinflammatory genes like MCP-1, TNFα, vascular cell adhesion molecule-I (VCAM I), intercellular adhesion molecule-I (ICAM I), and interferon-γ (IFNγ).


PPARγ is considered the master regulator of adipogenesis, and has been extensively studied in the context of obesity. At least two different isoforms of PPARγ are known: PPARγ1, which is the form expressed in nonadipose tissues, and PPARγ2, which is adipose-tissue specific. Unsaturated fatty acids and several eicosanoids serve as endogenous agonists of PPARγ, while antidiabetic drugs, the thiazolidinediones, act as synthetic agonists. Target genes of PPARγ are involved in adipocyte differentiation, lipid storage, and glucose metabolism. PPARγ activation strongly reduces inflammatory gene expression.

 

Compared to PPARα and PPARγ, much less is known about PPARβ/δ and its natural ligands.Hence its role has been poorly explored. PPARβ/δ has been directly linked to the development of obesity. Due to the anti-inflammatory properties of PPARβ/δ in macrophages, it is plausible that atherosclerosis is affected by PPARβ/δ-activation. Whether, the biological effects of PPARs are because of inhibiting inflammation, remains to be determined.

Assis. Prof. Dr. Yongsoo Park,

"MicroRNA exocytosis by vesicle fusion as a novel neuromodulator"

By combining interdisciplinary techniques that include cell biological, biophysical, and biochemical tools, we aim to investigate the molecular mechanisms of microRNA (miRNA) exocytosis. Although non-coding RNA (ncRNA) that include miRNA regulates gene
expression inside the cell where they are transcribed, extracellular RNA has been recently discovered outside the neurons. Using next-generation RNA sequencing, vesicle purification techniques, and synthetic neurotransmission, we observed that LDCVs contain a variety of miRNAs including miR-375. miRNA exocytosis is mediated by the SNARE complex and accelerated by synaptotagmin-1, a Ca 2+ sensor. Our results are opening the new field and concept that miRNA can be a novel neuromodulator, which is stored inside the vesicle and released together with classical neurotransmitters by vesicle fusion, thereby contributing to cell-to- cell communication.

Prof. Dr. Minoo Rassoulzadegan,

"RNA-mediated epigenetic heredity: experimental mouse models of an acquired pathology"

We reported over the recent years several instances of non-Mendelian heredity in the mouse (paramutations). Transcriptional upregulation of major control loci resulted either in fur color variation (Kit gene), heart hypertrophy (Cdk9 gene), or in increased body size and cognitive ability (Sox9). Experiments involving microinjection of purified RNAs in fertilized eggs had led us to the conclusion that sperm RNA was the transgenerational vector of these epigenetic states. We further observed a requirement for cytosine methylation by the Dnmt2 methyltransferase at defined sites in the inducer and target RNAs [1-4]. Further examples of sperm RNA-mediated inheritance were recently reported by others, namely a distinct instance of the Kit paramutation [5] and heritable neuropathological conditions [6, 7]. Transgenerational determination by sperm RNA provides theoretical grounds for several unexplained but well documented instances of non Mendelian paternal heredity and suggests experimental approaches. We will report mouse models of paternal RNA-mediated determination pertinent to two pathologies, hereditary transmission of the diet-induced metabolic syndrome (obesity, type 2 diabetes) [8, 10] and the paternal control of the length of telomeres and of the telomere diseases [9].


1. Rassoulzadegan, M., et al. Nature, 2006. 441(7092): p. 469-74.
2. Wagner, K.D., et al. Dev Cell, 2008. 14: p. 962-969.
3. Grandjean, V., et al. Development, 2009. 136(21): p. 3647-55.
4. Kiani, J., et al. PLoS genetics, 2013. 9(5): p. e1003498.
5. Yuan, S., et al. Sci Rep, 2015. 5: p. 9266.
6. Gapp, K., et al. Nature Neurosci, 2014. 17(5): p. 667-9.
7. Rodgers, A.B., et al. Proc Natl Acad Sci U S A, 2015. 112(44): p. 13699.
8. Rando, O.J. and R.A. Simmons. Cell, 2015. 161(1): p. 93-105.
9. Armanios, M. and E.H. Blackburn. Nature Reviews. Genetics, 2012. 13(10): p. 693-704
10. Chen, Q. et al. Science, doi:10.1126/science.aad7977 (2015).

Dr.Christopher Mayack,

"Ecology, evolution and animal behavior"

Robert Trivers once said, “everybody has a social life”, but even though social behavior is quite pervasive throughout the animal kingdom and humans demonstrate highly social behavior, a dedicated field to the study of it wasn’t really recognized until Edward O. Wilson coined the term ‘Sociobiology’. This talk will focus on two approaches used to study the evolution of social behavior.
The first will focus on discussing the underlying proximate mechanisms (genes, hormones and neurobiology) that gives rise to social behavior. The second will address how this first approach is integrated with studying why social behavior has evolved, which turns to understanding the function of the behavior and aims to find an adaptive explanation. I will discuss the theoretical underpinnings used to explain how it is that being social behavior may or may not lead to an increase in fitness. I will also discuss a range of taxa, from bacteria to humans, to draw common themes as it has evolved independently, multiple times, throughout evolutionary history.

Assis. Prof. Dr. Andres Aravena,

"Bioinformatics + Biotech in high impact strategic industries"

Biotechnology has changed a lot in the last 10 years, and it will probably keep changing. The same is true in general for all science and technology. Experiments that used to be expensive and slow, are today cheap and fast. Producing and analyzing huge volumes of data is easy and inexpensive. Everybody can build new instruments, or cheaper versions of the standard instruments at home, and even do synthetic biology in any lab. How are you going to succeed in this brave new world?

 

In this talk we will speak about some of the challenges that you as a biotechnologist will face in the following years, and what we can learn from  previous experiences (if possible). We will show the case of Chile, where biotechnology is used for the rational exploitation of natural resources (mainly copper, but also wood, fishes, fruits and wine), which are the main source of national income. Biotechnology has been essential for the efficient use of resources,  transforming the industries and have a huge positive effect on the whole economy.

 

A key part of this successful biotechnological experience is due to bioinformatics and computational biology. Using mathematical and informatic tools allows us to design the best experiments, simulate the possible outcomes and extract meaningful knowledge from the results.

Assis. Prof. Dr.​ Andrew Harvey,

"Plant Cell Wall Biotechnology: Perspectives and Future Directions"

Plants, both as a whole and at the cellular level, are defined by the size, shape, and thickness of their cell walls. These walls are primarily made up of cellulose and non-cellulosic polysaccharides which represent the largest source of renewable carbohydrates in the world. The ever-rising global need for energy makes the fermentable sugars present in these carbohydrates a desirable goal for creating renewable liquid transport fuels. In addition, the polysaccharides of the plant cell wall are essential components of the diet as dietary fibre, particularly those of certain cereal grains, and their roles in reducing the incidence of diseases such as type II diabetes, cardiovascular disease, colorectal cancer, and inflammatory bowel diseases. Other areas of study on plant cell walls include their use in biofibers, paper and pulp industry biomaterials, sustainable construction, bioplastics, sustainable agriculture,  bioactive molecules, biocontrol, pharmaceutical industry, and nutraceuticals. An overview of current plant cell wall research will be given and possible future directions explored.

Assoc. Prof. Ralph Meuwissen,

"Biology and Molecular Therapy of Lung Cancer"

Although in the last 30 years much scientific progress has been made in understanding some of the genetics, molecular and cellular biology of lung cancer, this did not result in lowering the mortality rate for lung cancer which is still the highest for any cancer around the world (and certainly for Turkey). In our lab, we focus mainly on the research of Small Cell Lung Cancer, the most lethal form of human lung cancer.


In the last decade, vast scientific progress has been made in genetic characterization of SCLC, which led to development of genetically engineered mouse models (GEMMs) that closely mimic human SCLC However, current SCLC models such as cultured clonal tumor cell lines and GEMMs poorly represent the complex genetic heterogeneity of human SCLC. We therefore also include human primary SCLC samples in patient derived xenotransplant (PDX) models for thorough genetic analyses and as basis for testing
immunotherapeutic approaches against SCLC.


The Meuwissen lab research consists of 3 main thematics:
- Characterize the tumor plasticity in SCLC during tumor onset progression and (chemo)therapy response
based on SCLCs from GEMMs and/or human PDXs Full cellular heterology of tumor lesions will be
examined and subpopulations will be characterized through genetic analyses, specific growth and
marker characteristics leading to the unravelling of molecular mechanism governing epithelial
mesenchymal transition and drug resistance.


- Human SCLC PDXs are maintained on humanized mice background. These mice with fully activated
human adaptive human response will serve as platform for immunotherapeutic research against SCLC.


- Applying latest techniques of liquid biopsy dependent analyses of circulating tumor DNA and RNA for
diagnostic and therapeutic purposes.


In conclusion, our studies should provide us with a better understanding of the phenotypic complexity of
SCLC and its implications for comprehending the underlying molecular and cellular mechanisms that
govern SCLC metastatic behavior, drug resistance and evasion of an adaptive immune response.
Moreover, our new SCLC PDX models will be of valuable use for extensive drug screens and should
thereby lead to discover new candidate genes that control some of these pivotal molecular pathways.
Our combined results therefore will improve the design of new, more efficient (immuno)targeted- and
chemo- therapeutic approaches against SCLC.

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