Apparently there’s a beta Bioinformatics group on Stack Exchange now. It’s just come out of alpha in the last few days and it appears anyone can join now.
Epigenetics refers to information transmitted during cell division other than the DNA sequence per se, and it is the language that distinguishes stem cells from somatic cells, one organ from another, and even identical twins from each other. In contrast to the DNA sequence, the epigenome is relatively susceptible to modification by the environment as well as stochastic perturbations over time, adding to phenotypic diversity in the population. Despite its strong ties to the environment, epigenetics has never been well reconciled to evolutionary thinking, and in fact there is now strong evidence against the transmission of so-called “epi-alleles,” i.e. epigenetic modifications that pass through the germline.
However, genetic variants that regulate stochastic fluctuation of gene expression and phenotypes in the offspring appear to be transmitted as an epigenetic or even Lamarckian trait. Furthermore, even the normal process of cellular differentiation from a single cell to a complex organism is not understood well from a mathematical point of view. There is increasingly strong evidence that stem cells are highly heterogeneous and in fact stochasticity is necessary for pluripotency. This process appears to be tightly regulated through the epigenome in development. Moreover, in these biological contexts, “stochasticity” is hardly synonymous with “noise”, which often refers to variation which obscures a “true signal” (e.g., measurement error) or which is structural, as in physics (e.g., quantum noise). In contrast, “stochastic regulation” refers to purposeful, programmed variation; the fluctuations are random but there is no true signal to mask.
This workshop will serve as a forum for scientists and engineers with an interest in computational biology to explore the role of stochasticity in regulation, development and evolution, and its epigenetic basis. Just as thinking about stochasticity was transformative in physics and in some areas of biology, it promises to fundamentally transform modern genetics and help to explain phase transitions such as differentiation and cancer.
This workshop will include a poster session; a request for poster titles will be sent to registered participants in advance of the workshop.
Adam Arkin (Lawrence Berkeley Laboratory)
Gábor Balázsi (SUNY Stony Brook)
Domitilla Del Vecchio (Massachusetts Institute of Technology)
Michael Elowitz (California Institute of Technology)
Andrew Feinberg (Johns Hopkins University)
Don Geman (Johns Hopkins University)
Anita Göndör (Karolinska Institutet)
John Goutsias (Johns Hopkins University)
Garrett Jenkinson (Johns Hopkins University)
Andre Levchenko (Yale University)
Olgica Milenkovic (University of Illinois)
Johan Paulsson (Harvard University)
Leor Weinberger (University of California, San Francisco (UCSF))
Abstract: Despite the obvious advantage of simple life forms capable of fast replication, different levels of cognitive complexity have been achieved by living systems in terms of their potential to cope with environmental uncertainty. Against the inevitable cost associated to detecting environmental cues and responding to them in adaptive ways, we conjecture that the potential for predicting the environment can overcome the expenses associated to maintaining costly, complex structures. We present a minimal formal model grounded in information theory and selection, in which successive generations of agents are mapped into transmitters and receivers of a coded message. Our agents are guessing machines and their capacity to deal with environments of different complexity defines the conditions to sustain more complex agents.
I just found out about this from John Carlos Baez and wish I could go! How have I not managed to have heard about it?
November 16, 2016 – November 18, 2016
Noyce Conference Room
This workshop will address a fundamental question in theoretical biology: Does the relationship between statistical physics and the need of biological systems to process information underpin some of their deepest features? It recognizes that a core feature of biological systems is that they acquire, store and process information (i.e., perform computation). However to manipulate information in this way they require a steady flux of free energy from their environments. These two, inter-related attributes of biological systems are often taken for granted; they are not part of standard analyses of either the homeostasis or the evolution of biological systems. In this workshop we aim to fill in this major gap in our understanding of biological systems, by gaining deeper insight in the relation between the need for biological systems to process information and the free energy they need to pay for that processing.
The goal of this workshop is to address these issues by focusing on a set three specific question:
- How has the fraction of free energy flux on earth that is used by biological computation changed with time?;
- What is the free energy cost of biological computation / function?;
- What is the free energy cost of the evolution of biological computation / function.
In all of these cases we are interested in the fundamental limits that the laws of physics impose on various aspects of living systems as expressed by these three questions.
Purpose: Research Collaboration
SFI Host: David Krakauer, Michael Lachmann, Manfred Laubichler, Peter Stadler, and David Wolpert
Analysis of phase 1 and 2 trials testing the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.
I built the microinjectors used in these experiments for injecting stem cells into the first human patients.
Links to some earlier articles:
- First U.S. stem cells transplanted into spinal cord | CNN.com (January 2010)
- Stem cell treatment goes from lab to operating room | CNN.com (May 2010)
Transplantation of spinal cord–derived neural stem cells for ALS
Analysis of phase 1 and 2 trials
Authors: Jonathan D. Glass, MD; Vicki S. Hertzberg, PhD; Nicholas M. Boulis, MD; Jonathan Riley, MD; Thais Federici, PhD; Meraida Polak, RN; Jane Bordeau, RN; Christina Fournier, MD; Karl Johe, PhD; Tom Hazel, PhD; Merit Cudkowicz, MD; Nazem Atassi, MD; Lawrence F. Borges, MD; Seward B. Rutkove, MD; Jayna Duell, RN; Parag G. Patil, MD; Stephen A. Goutman, MD; Eva L. Feldman, MD, PhD
Objective: To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers.
Methods: This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale–Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups.
Results: Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression.
Conclusions: Intraspinal transplantation of human spinal cord–derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers.
Classification of evidence: This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues.