Egidio D’Angelo, MD, Ph.D.
Full Professor of Physiology & Director, Brain Connectivity Center, University of Pavia, Italy
Realistic modeling: new insight into the functions of the cerebellar network
Realistic modeling is an approach based on the careful reconstruction of neurons synapses starting from biological details at the molecular and cellular level. This technique, combined with the connection topologies derived from histological measurements, allows the reconstruction of precise neuronal networks. Finally, the advent of specific software platforms (PYTHON-NEURON) and of super-computers allows large-scale network simulation to be performed in reasonable time. This approach inverts the logics of older theoretical models, which anticipated an intuition on how the network might work. In realistic modeling, network properties “emerge” from the numerous biological properties embedded into the model.
This approach is illustrated here through an outstanding application of realistic modeling to the cerebellar cortex network. The neurons (over 105) are reproduced at a high level of detail generating non-linear network effects like population oscillations and resonance, phase-reset, bursting, rebounds, short-term and long-term plasticity, spatiotemporal redistrbution of input patterns. The model is currently being used in the context of he HUMAN BRAIN PROJECT to investigate the cerebellar network function.
Correspondence should be addressed to
Dr. EgidioD’Angelo,
Laboratory of Neurophysiology
Via Forlanini 6, 27100 Pavia, Italy
Phone: 0039 (0) 382 987606
Fax: 0039 (0) 382 987527
dangelo@unipv.it
Acknowledgments
This work was supported by grants from European Union to ED (CEREBNET FP7-ITN238686, REALNET FP7-ICT270434) and by grants from the Italian Ministry of Health to ED (RF-2009-1475845).
Leland H. Hartwell Ph.D.
2001 Nobel Laureate, Physiology & Medicine
Dr. Lee Hartwell received the 2001 Nobel Prize in Physiology / Medicine for his discovery of protein molecules that control the division of cells. He was the President and Director of the Fred Hutchinson Cancer Research Center in Seattle, Washington before moving to Arizona State University’s Center for Sustainable Health.
Dr. Hartwell is also adjunct faculty at Amrita University. He spoke to the delegates at Bioquest from his office in the US, over Amrita’s e-learning platform A-View. Given below are excerpts from his address.
I would like to address the young people in the audience. I know that many of you may have come to this meeting wondering, “How can I become a successful scientist? How can I prepare myself to make a contribution in this world?”
These questions are interesting to me also.
Believe it or not, I am still trying to be a successful scientist. That may surprise you since you probably think that a Nobel laureate must have found the answers. But the problem is that the answers to these questions change with time and the answers are different today than what they were when I began my career fifty years ago. The strategy of the 1960’s doesn’t work so well anymore. What is different now?
First, what we know now is much more. For example, by 1970, no genes from any organisms were sequenced. In 2013, we have the complete sequence of the human genome. Second, not only do we know much more today, accessing that knowledge is easy. Third, obtaining new information is much faster today.
Our rich understanding of science and technology is now needed to solve many serious problems. The human population has reached the size where we are utilizing all available resource of the planet. We are utilizing all of the agricultural land, all of the water, all of the forest and fishing resources. We are also polluting the planet that we live on.
We are polluting the land with fertilizers and pesticides; the oceans with acids and the atmosphere with carbon dioxide. We are using up top soil and ground water, thereby reducing our capacity to feed ourselves. We are using up petroleum, the energy source that our entire economy is dependent on. These are problems we were largely unaware of, fifty years ago. But these are problems that must be solved in your life times.
The big question facing your generation is, how can human beings live sustainably on planet earth. Your two broad goals on sustainability are 1) leave the planet as you first found it for your future generations; don’t use up the resources and don’t pollute the planet 2) everyone deserves to have an equal share of the earth’s resources.
Income strongly determines one’s opportunities in life. Many poor people succumb to chronic diseases and unhealthy environments. This inequality undermines our ability to live sustainably. We can’t ask the poor to leave the planet as they found it if they can’t support their families. Education, healthcare, employment are essential to having a sustainable society.
How can we be a successful scientist in 2013?
1. First choose a problem to solve
2. Ask questions to understand why it is not solved
3. Collaborate with those who can help
4. Develop a solution that works in the real worldChronic diseases are our major burden and this burden will get worse. Heart disease, diabetes, cancer, dementia and other diseases. The good news is that the chronic diseases are largely preventable and more easily curable if detected early. One question that attracts me is how can we detect disease earlier when it can be more easily cured?
Can we use our increasing knowledge in molecular biology to identify biomarkers for early disease detection?
We need to collaborate very closely with clinicians who care for patients to find out exactly where they need help.
I think if we apply our technology to important clinical questions we will actually save medical expenditure and be well on our way to making a great contribution to society.
Andrey Panteleyev, Ph.D.
Vice Chair, Division of Molecular Biology, NBICS Centre-Kurchatov Institute, Moscow, Russia
The system of PAS proteins (HIF and AhR) as an interface between environment and skin homeostasis
Regulation of normal skin functions as well as etiology of many skin diseases are both tightly linked to the environmental impact. Nevertheless, molecular aspects of skin-environment communication and mechanisms coordinating skin response to a plurality of environmental stressors remain poorly understood.
Our studies along with the work of other groups have identified the family of PAS dimeric transcription factors as an essential sensory and regulatory component of communication between skin and the environment. This protein family comprises a number of hypoxia-induced factors (HIF-alpha proteins), aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT), and several proteins implicated in control of rhythmic processes (Clock, Period, and Bmal proteins). Together, various PAS proteins (and first of all ARNT – as the central dimerization partner in the family) control such pivotal aspects of cell physiology as drug/xenobiotic metabolism, hypoxic and UV light response, ROS activity, pathogen defense, overall energy balance and breathing pathways.
In his presentation Dr. Panteleyev will focus on the role of ARNT activity and local hypoxia in control of keratinocyte differentiation and cornification. His recent work revealed that ARNT negatively regulates expression of late differentiation genes through modulation of amphiregulin expression and downstream alterations in activity of EGFR pathway. All these effects are highly dependent on epigenetic mechanisms such as histone deacetylation. Characterisation of hypoxia as a key microenvironmental factor in the skin and the role of HIF pathway in control of dermal vasculature and epidermal functions is another major focus of Dr. Panteleyev’s presentation.
In general, the studies of Dr. Panteleyev’s laboratory provide an insight into the PAS-dependent maintenance of skin homeostasis and point to the potential role of these proteins in pathogenesis of environmentally-modulated skin diseases such as barrier defects, desquamation abnormalities, psoriasis, etc.