Wednesday, December 05, 2012

Thinking about inheritance and epigenetics



There is an interesting RadioLab podcast on inheritance that is worth listening to.  It discusses the differences between Darwinian and Lemarckian mechanisms of inheritance and more.  

They discuss the case of the midwife toad and the work of Paul Kammerer.  One part of this involved work that suggests the role of epigenetic inheritance (changes that do not involve mutations in the DNA, but rather hereditable changes in gene expression.)   

The whole idea of the "Central Dogma" associated with molecular biology (namely that information moves from DNA to RNA to protein, but not backward from protein to nucleic acid, seems pretty clear.  BUT, it is also true that a behavior can influence selection.  This is the topic of the book and the video lecture: Evolution in four dimensions. by Eva Jablonka and Marion J. Lamb.

Sadly, there are some errors in the Radiolab: Inheritance pod cast.  For example that methyl groups are "sticky", and that the transcription factors "knock off" methyl groups is weird (and wrong, at the molecular level).  Both processes are mediated by enzymes (histone methyltransferases and demethylases).  In fact, there are a number of modifications of chromatin, all of which are enzymatically mediated.  

Also interesting is the RadioLab episode on Stochasticity.  The section that starts around 43 minutes in is relevant to gene expression.  



Wednesday, November 07, 2012

MadSci Network: Does the DNA contain the codes needed for shaping body organs?

I love composing answers for the MadSci Network and here is my latest here [link].

The challenge to answering such questions is to try and place the answer in a coherent and accessible context.  While it is hard to know whether a particular answer actually succeeds in doing that, it certainly gets one thinking about how to address complex questions and looking around for compelling references and resources.

For this answer, I found an amazing video on polydactyl, which could be viewed as a beneficial mutation (assuming that six fingers and toes are better than five!) 

Sunday, October 28, 2012

Viruses within Viruses & the politics of Anti-Science

One of the more amazing discoveries of late are the giant viruses (first identified in 2003)(for more details, read reviews here and here).  These miniviruses have been found to infect various types of amoeba.  

More amazing still, these giant viruses have their own parasites [read general description here and a scientific description here.]   Cells infected with the giant virus are infected with a second type of virus, known as a virophage, which replicates only in virus infected cells.  Another example of how ecological niches, no matter how small or obscure, can be populated by replicating entities.  

On another, less intellectually entertainingly front, it is increasingly amazing how both scientific denialism and active anti-scientific posturing and policies are coming to dominate American political discourse, particularly in situations where they are seen to threaten fundamentalist religious doctrine (or in Boulder, CO, self-centered ignorance, as illustrated by the anti-vaccine and anti-GMO movements)[check out the panic virus blog].  

This recent article Shawn Otto in Scientific American (Antiscience beliefs jeopardize U.S. democracy) is particularly cogent.  In part scientific denialism may arise from the naive view that science equals truth, and so poses a direct threat to belief and in part from a failure of our education system to help students understand the process by which science accumulates and integrates useful knowledge into a coherent world view. Perhaps more emphasis on critical analysis and less on often superficial "inquiry" would help here.  

In any case, it is scary to see the US return (at least in certain regions) to medieval patterns of thought -- I wonder when witch burning will become part of a political party's platform.  Probably not long, given political positions that explicitly deny global warming [read more here].   




Sunday, October 07, 2012

Is embryology a lie "straight from the pit of hell"?

Two remarkable stories from today's paper, one about a Republican Georgia representative  Paul Broun who appears to believe that, 


"All that stuff I was taught about evolution and embryology and
Big Bang theory, all that is lies straight from the pit of hell. "
What is truly bizarre is that this person on the House Science, Space and Technology committee.    I am particularly confused by, and would love to understand the logic behind, the  relationship between embryology and hell.  

The second is a quote from an Arkansas state representative John Hubbard that slavery was a blessing in disguise and that all Muslims should be deported, similar views appear to be held by Republican state house candidate Charlie Fuqua.  Their views on Mormons, Jews, atheists, and perhaps all Democrats, etc, are not recorded, but Fuqua claims that 


"I think my views are fairly well-accepted by most people".  

Also finished an interesting book that is relevant, "The Rocks Don't Lie: A Geologist Investigates Noah's Flood" by D.R. Montgomery.   


Saturday, September 22, 2012

Evolutionary contingency (in the lab)

Bount et al (2012) describes a very interesting study of the appearance (evolution) of the ability of the common gut bacteria, E. coli, to utilize citrate in the presence of O2, something that E. coli normally cannot do. This work was based on the original observation that described the evolutionary origin of citrate utilizing E. coli (Bount et al., 2008).  The Lenski lab has been growing (and freezing) samples of this population for over 40,000 generations (here is an interesting paper on how these populations have been used to study competition within a population (Le Gac et al., 2012).  

The evolution of the ability to utilize citrate in the presence of O2 in E. coli involved "potentiating mutations", which occurred in one specific lineage somewhere around the 20000th generation of the experiment.  These mutations have no (as yet discovered) overt phenotype on their own. 

Later on in this lineage, around the 31,000th generation, there was a mutation that involved the duplication and generation of a novel fusion protein derived from the citrate-succinate antiporter (a membrane-transport protein of a type we discuss generically here in biofundamentals).  This mutation allows the cell's carrying it to import and grow (albeit) poorly on citrate.  Subsequent mutations improve the efficiency of citrate metabolism.  

What is interesting is that because they had "frozen ancestors", Blout et al could "replay" their evolution, and ask, when new citrate utilizing lines arose (which they did), whether they had similar (although not identical) mutations to that found in the originally identified lines.  Interestingly, they did.  

Now it becomes an interesting question whether, given that E. coli is usually defined in part by its inability to grow on citrate under aerobic conditions, whether the appearance of cells, derived from E. coli, but able to grow on citrate in the presence of O2 represents a new species or not.  



Saturday, September 15, 2012

Evolutionary thinking and "just so" stories

It is all to easy to tell satisfying stories about how various traits have come to be:  here Anthony Gottlieb in the New Yorker writes about just so stories about the origins of human behavior (and consciousness).

The essay makes a number of points that I have tried to emphasize in class and is worth reading.

Thursday, September 13, 2012

Thinking about sexual dimorphism (again)

Well, here is a particularly dramatic example of sexual dimorphism, a new species of monkey identified in the Congo (and described in the NYT) and an interesting quote, "And adult males have a huge bare patch of skin in the buttocks, testicles and perianal area,” said John A. Hart, the researcher who described the coloring. “It’s a brilliant blue, really pretty spectacular.”" Now I wonder why?

Monday, September 10, 2012

Out of Africa, Mitochondrial Eve and Nuclear Adam


  Here is an article by CAMPBELL & MISHKOFF (2008) on genetic diversity in Africa and a current view on human migration out of African that you might find interesting.

The video is a cleaned up version of the original video, so as to remove (most) gratuitous insults. 

Monday, August 27, 2012

The weird connections between things

or why life is counter-intuitive: this story (in the New York Times [link] ) indicates that bacterial and parasite infection (common in the "native" state of humans, but increasingly rare in modern, "hygenic" societies) helps modulate our immune and inflammatory systems.  

In a world where we are shielded from such chronic infections, we are more sensitive to "out of control" inflammatory responses, which in turn lead to diseases as asthma and autism.   In a weird way, being sick (or infected) keeps us from getting sick.  

Sunday, August 26, 2012

Teaching the young (and old).

Studies on brain development development indicate the people's brains continue to change through their 20s.  Moreover, it is worth remembering that the very process of learning (rather than remembering) takes time and practice.

It is possible to remember, quite vividly, one time events, but mastering hard ideas, skills, etc., takes repetition.   (One reason sports teams and athletes practice so much!)

Tuesday, March 20, 2012

Teaching evolution: seminar in EBio, 23 March 2012



This is scheduled for the last day before spring break, and I am working (between reviewing and reading) to put together something different from a conventional seminar - more educational, entertainingly, and provocative than most (we shall see).  

Sunday, February 19, 2012

Autism and Vaccination

Reading "The Panic Virus" at the recommendation of a student,  I find myself recommending it to others - it is absorbing (with few scientific mistakes, those that are there are early on and involve how immune responses are generated at the molecular level, a complex subject.)

The issue of autism presents quite a disturbing case study of the difficulties faced by science educators in the context of serious real world (and deeply emotional) issues.  It raises questions about how to maintain an understanding of the value of vaccination in the absence of disease (because vaccination works), the idea of the social value of a treatment versus personal risk, the search for causes of a disease (autism) in the absence of clear data or plausible mechanism (is it one or multiple diseases?), and the proliferation of psuedo

Now there is a preliminary study that suggests autism's symptoms can begin quite early in life.  As usual in science, not to be taken too seriously unless it is independently replicated.

Monday, January 16, 2012

Teaching with Technology... Fall 2011 - Reflection


Making course materials more deeply digital (and Socratic)     Mike Klymkowsky


One of (but certainly not the only) interesting aspect of the Fall 2011 Teaching with Technology group was to see the various ways faculty approach teaching, the assessment of student learning (that is, the effectiveness of their teaching), and their various concerns and aspirations. Even though I thought I had thought a lot about this topic, I quickly realized that there were many tools, techniques and overall approaches that I had not given serious consideration (if I had considered them at all).  Here I will outline my own approaches and the plans I have to incorporate newly learned strategies into the design and delivery of the courses I will be teaching during 2012.  

Making Biofundamentals more “deeply digital”: Over the decades I have been teaching, one of the issues that has always troubled me is the fact that students rarely read the assigned materials prior to class.  This situation was not helped by the fact that the textbooks available for the topics I was called upon to teach rarely seemed (at least to me) to approached those topics in a logical and cogent manner.  A particular example involves MCDB 1150 - Introduction to Molecular Biology.  Its structure seemed “upside-down” to me, essentially ignoring an evolutionary perspective and mechanisms, and often introducing irrelevant facts, rather than concentrating on key ideas, and then applying those ideas to various scenarios.  Since an understanding of evolutionary mechanisms (a difficult topic in its own right) seems essential to making sense of the structure and behavior of biological systems [1], the almost complete absence of evolutionary biology in MCDB 1150 was a serious concern (particularly since evolutionary mechanisms are not explicitly addressed anywhere else in the current MCDB curriculum).  At the same time, I found myself deeply dissatisfied by the laboratory courses associated with the three introductory MCDB courses; in part because of their lack of justification in terms of learning outcomes and because they consumed resources that might be better used for more intensive upper division lab courses.

It was in this light that during a sabbatical year, I decided to address some of these issues by developing virtual labs (which I will not discuss further here) and a new Introductory course,  Biofundamentals (http://virtuallaboratory.colorado.edu/Biofundamentals/).  This course (MCDB 1111: Biofundamentals) was approved as a replacement for the standard lecture/lab sequence.

What was clear, however, was that it was no easier to get students to read the Biofundamentals materials before class than it was for a traditional textbook - students simply did not expect to have to read the materials before class, didn’t, and I did not have the energy or disposition to set up mechanisms to attempt to insure that they did the reading, e.g. reading quizzes, primarily because I knew I would not be able to respond to such quizzes in a timely manner.  I  adapted to non-reading. 

As I was preparing to teach Biofundamentals again, now as a section of MCDB 1150, two factors led me to rethink how the course should be taught.  The first was the experience of developing a new introductory chemistry curriculum with Melanie Cooper (Clemson University), Chemistry, LIfe, the Universe, and Everything (CLUE: http://besocratic.colorado.edu/CLUE-Chemistry/), and the second was learning about new web-based approaches to driving student interactions with text. Two approaches appeared to be the most promising, nota bene (http://oeit.mit.edu/category/keywords/nota-bene) developed at MIT and focussed on interactions with pdfs and Highlighter.com (http://highlighter.com/), which initially worked with HTML pages, and has recently extended to pdfs through its
HTML5 reader.  The Highlighter system (which is still very much in a beta-form) allows an instructor to divide a class into groups; students can comment on, and respond to the comments from other students.  Comments are visible to both students and the instructor.  The system has (at least in theory) the possibility of compelling students not only to read, but to engage with the text and each other students prior to class.  
To further encourage engagement, the Biofundamentals materials have embedded within them “Questions to Answer” and “Questions to Ponder”, which each group needs to be sure it has answered before coming to class.  Since I received email notification of each comment and response, I could quite easily get an impression of what concepts the students were having difficulty with, and which were deeply misunderstood.  This enabled me to focus in-class discussion on the harder ideas.   

Analysis of student interactions with the text and each other is something simply not possible with traditional texts, and offers the very real option of evolving the text over time, to more explicitly engage students.  My current plan is to review these comments as part of editing the Biofundamentals website this summer. 

Adding resources to Biofundamentals through web-casts. One idea that particularly attracted my attention was the use of webcasts to capture short presentations, which students could then review at their leisure.  I am currently planning to make some of these for the next version of Biofundamentals, and plan to compare Camtasia and the web-based Screencast-o-matic (http://www.screencast-o-matic.com/) in terms of ease of use and effectiveness. 

This semester, I am teaching MCDB 4811/5811 Teaching and Learning Biology (which serves as an elective in MCDB and a requirement for the CU Teach science and mathematics teacher certification program).  
After a very interesting conversation with Lorrie Shepard, Dean of the School of Education, on using teaching as a means to assess student understanding, I am planning to have students use Screencast-o-matic to develop 10 to 15 minute webcasts of specific "key concept" lessons.  We will then analyze these lessons in class in order to better understand how various topics might best be approached (and as a way of revealing the presenters’ own understanding of those topics).

Adding formative (BeSocratic) assessments to Biofundamentals.   Working with Melanie Cooper, Sam Bryfczynski, and Josiah Hester at Clemson University, we have developed a novel web/tablet-based graphics-centered formative assessment system, BeSocratic (http://besocratic.clemson.edu/).   The system allows instructors to develop activities in which students respond to questions graphically (and textually).  For example, students can be asked to graph the behavior of a gene network [2], the progression of an epidemic, the distribution of kinetic energies in a system, or the potential energy between atoms or molecules.   Rules can be set, and linked to specific feed-back prompts, in the form of questions (e.g. What were you assuming when drawing your graph).  The system is flexible, in addition to graphs, students can work with molecules and various types of drawings and schematics to illustrate their ideas.  In addition, the system captures all of the students’ inputs which allows for post-instructional analyzes to determine how well various activities worked, in the context of students assumptions.

When teaching Biofundamentals last semester, I introduced a number of graphics-based assignments, through which students could be asked to reveal, and then reflect upon their assumptions (and their implications).  This Socratic (metacognitive) approach revealed some interesting student assumptions which I would never have appreciated.   As an example, it became clear that many students assumed that when a transcription factor bound to the regulatory region of a gene, it was “used up”.  One of my goals during the spring and summer is to generate and test a number of BeSocratic activities that address key ideas associated with Biofundamentals.  This is part of a larger NSF-funded project to develop and test beSocratic activities in chemistry, physics, biology, and mathematics.  In particular, I am collaborating with Eric Stade (Mathematics) to develop beSocratic activities for MATH 1310: Calculus, Stochastics and Modeling, a course that we hope will eventually replace Math 1300: Calculus I, for most chemistry and biology students.

Designing an assessment for the efficacy of the Biofundamentals course.  While including technological innovations into one’s teaching may well be valuable, this is certainly not a given.  Assuming that the goal of courses and instruction is student learning, the process of evaluating the value of technological innovations must be whether they help students learn more and better.  This, of course, requires that we specify what we expect students to learn, and what we expect them to be able to do with that new understanding.  Assessing student learning (and course and curricular effectiveness) is certainly not easy.  There is no University requirement that courses (or perhaps more surprisingly, the overall curriculum) specify their learning goals in a way that makes independent, objective assessment possible (I take it as a given that the instructor is not in a position to provide some objective assessment, since they are (hopefully) emotionally engaged in the course). 

In the context of Biofundamentals, there are some factors that favor at least a comparative evaluation of course effectiveness.  As currently presented, Biofundamentals is a distinct version of the introductory course in MCDB (MCDB 1150).  All MCDB students currently have to take the associated laboratory course (MCDB 1151), no matter which flavor of the “lecture” course they take.  By working with the instructors of the other sections of MCDB 1150, my intention is to develop a common assessment that can be administered in the laboratory course.  The style of the assessment will be questions requiring short essay responses; these will be evaluated using a rubric, described in Henson et al [3] in which correct, incorrect, and irrelevant responses are tallied, so as to provide a clearer picture of student thinking.   
 Literature cited:
1. Dobzhansky, T., Nothing in Biology Makes Sense Except in the Light of Evolution. Amer. Bio. Teach, 1973. 35: p. 125-129,.
2. Trujillo, C., M.M. Cooper, and M.W. Klymkowsky, Graph-based assessments, Socratic tutorials & students' thinking about molecular networks. BAMBED, 2012. in press.
3. Henson, K., M.M. Cooper, and M.W. Klymkowsky, Turning randomness into meaning at the molecular level using Muller’s morphs. Biology Open, 2012. in press.

Saturday, January 14, 2012

Arguing with "philosophers"

Rather late in the day I have come to recognize that when I responded to Brad Monton (a few years ago) regarding his defense of intelligent design/creationism, I was not speaking in the correct language. Alan Sokol's essay on this topic here seems much more to the point.

Luckily, I think I have gotten clearer about the practcal barriers to understanding evolutionary mechanism.