Interesting People I Have Met: E. Michael Ostap, Ph.D.


EDIT: I have updated the section below on the animation by Drew Berry.
EDIT 2: Please see the comment below from Dr. Ostap and my reply to him. Also see the revision in this OP regarding my discussion of ‘brilliant’ machines in the cell.

I met Dr. Ostap on a flight from Philadelphia to San Antonio. He sat next to me on this flight, and for the first portion of the flight was reading and scanning some sort of technical journal – it looked to me to be a medical journal. He then took out his laptop and for the remainder of the flight was immersed in some fascinating looking web sites, and some animations that I had seen before. I didn’t want to disrupt his work/study, but at one point I  interrupted him briefly and apologized for looking over his shoulder at what he was viewing.

The kinds of things the Dr. was looking at were obviously some micro-biology scenes, and similar to ones I had seen before and are featured in the videos below by Drew Berry and David Bolinsky.

In seeing these animations previously, I have wondered how they were produced and how accurate were they in depicting the activities of the cell.  Were these animations inferred somehow based on these scientists study of cellular activity, or were they the result of somehow direct observations via some sort of new and exotic microscopic-like instrumentation? My thoughts were that these sorts of cellular and DNA activities were beyond the capabilities of todays instrumentation.

So I was anxious to capture a  bit of Dr. Ostap’s time, but I didn’t want to interrupt his engrossment in his work – he was on his way to a conference, and was obviously doing a bit of last minute preparation.

So I sat there next to him fidgeting – closing my eyes to rest, but afraid that if I dozed off I would miss a chance to query him. So I opened an eye periodically to see if he had given up on his laptop … alas,  he was diligent in his work until time came when the announcement was made to shut down and put away all electronic equipment and computers … my time had finally come.

So I asked the Dr. If I could ask a few questions about him and his work, and he obliged and I was able to squeeze in a few questions in the limited time before the end of the flight. As you can see from his bio here,  Dr. Ostap is a Ph.D in Biochemistry, Molecular Biology, and Biophysics … a very well educated and smart man.

I asked him about the animations I had seen on his computer, and the animations such as shown in the videos below. How are they produced, are they accurate and are they the result of a great deal of inference or are they the result of some type of observations.  I’ll paraphrase his answers as best I can here, and hope that what I write is close to accurate statements of what I believe he was telling me:

The animations are for the most part the result of observations … today’s instrumentation is actually able to look into the cell and see much of what is going on. For example, in the walking machine called Kinesin seen in the videos below, we are able to actually see this machine walking on a type of roadway, and pulling along a load of cargo manufactured at one place in the cell to another place in the cell. The roadway is actually seen being constructed in front of the machine, and its de-construction is actually seen behind the machine as it moves along. So he affirmed that these animations are for the most part accurate representations of the types of activities of the cell and DNA.

These observations are programmed into a computer program, and as  new information and observations are obtained, the program is updated. The programs are also used to open up and stimulate further areas of research.

I asked him about the animations showing DNA replication and the error detecting and error correction mechanisms of this machine. Again, as best I can recall, he said these animations were the result of observations where they can actually see the replication of DNA.

In the case of DNA replication, be referred to this machine as a “brilliant machine.” I then asked him if this word – machines –  is how they describe the activities of the cell. He said Oh yes, they are machines.

He then briefly describes some of the work that his lab is engaged in. Here is an excerpt from his bio page:

“Description of Research
The goal of our research is to understand the cellular machinery responsible for powering cell movements and shaping the architecture of cells, tissues, and organs. Our discovery-based research focuses on the role of the cytoskeleton, molecular motors, and signaling pathways in powering cell migration, muscle contraction, and the transport of internal cell compartments. The pathways investigated in our laboratory are crucial for several normal and pathological processes, including: cell and tissue development, endocytosis, wound healing, immune response, cardiomyopathies, and metastases of tumors.
Most of our current efforts are focused on investigating cytoskeletal motors (myosin, dynein, and kinesin). These remarkable nano-machines use chemical energy stored in our cells (in the form of ATP) to generate mechanical force and motion. Cytoskeletal motors are the engines that power muscle contraction, cell migration, intracellular transport, cell division, and cell shape. We are determining how these motors work at the molecular level, how they are physically connected to the machinery they are powering, how they are regulated, how they interact with other motors and signaling networks, and how their fundamental biophysical parameters impact cell function. We are using a range of biochemical, cell biological, single-molecule, and other biophysical techniques to better understand these proteins in health and disease.”

A part of Dr. Ostap’s research has to do with the cellular machines associated with the muscular machines involved in hearing. This especially interests me because of my own history of Ménière’s disease and my loss of hearing in recent years – perhaps I’ll dig into this area and learn more about the muscles in my ears.

Dr. Ostap also suggested that I Google “systems biology” to learn more about the types of research going on in todays modern biology and medical research. I told him that I already had done so and will continue to search out new information.

So this very brief visit with Dr. Ostap was quite rewarding in that it confirmed some of my own thinking and layman-level research, as well as filling a few holes in my knowledge – and this from a well qualified man actively working in the fields of micro-biology.

And as I close this article, I leave you with a dictionary definition of “brilliant” as Dr. Ostap used the word in describing the “brilliant machines” working in our cells:

brilliant
adjective

  1. very bright : flashing with light
  2. very impressive or successful
  3. extremely intelligent : much more intelligent than most people

EDIT 2: I stand corrected by Dr. Ostap on my putting my preferred definition of Brilliant (3) into Dr. Ostap’s mouth, rather than definition 2 which aligns with his thinking. See his comment below.

Now I invite you to look at the videos below as well as others I have listed at:  A running List of Biological Evidences of Design in Nature in my own (this) blog …   I hope you enjoy them.

image

Drew Berry: Animations of unseeable biology | Talk Video | TED.com

Excerpt: And so what I’m about to show you is an accurate representation of the actual DNA replication machine that’s occurring right now inside your body, at least 2002 biology. So DNA’s entering the production line from the left-hand side, and it hits this collection, these miniature biochemical machines, that are pulling apart the DNA strand and making an exact copy. So DNA comes in and hits this blue, doughnut-shaped structure and it’s ripped apart into its two strands. One strand can be copied directly, and you can see these things spooling off to the bottom there. But things aren’t so simple for the other strand because it must be copied backwards. So it’s thrown out repeatedly in these loops and copied one section at a time, creating two new DNA molecules.


On further review of this amazing animation,  I looked at the comments to see what reactions others had, and for further comments and amplifications by Drew Berry. I recommend you do the same, but I would like to include a particular question and an answer by Drew. I will also list some of the links Mr. Berry points out for further reference and excitement …

arthur brogard

Posted 9 months ago

This is the greatest thing. I wonder if we could get more information as to the scientific accuracy of what is portrayed?

The sizes and shapes of the molecules – are they all guaranteed 100% correct? If not when what are the tolerances, just what should we bear in mind when watching?

The behavior of the molecules most especially those astounding ‘walking’ things – how were they arrived at? We can take it as real that’s how they look and how they operate?

Why/how do they operate like that? What causes a leg to swing forward and clamp on? And then why does it release?

And the contents of the cell – all that amazing crowd of structures and proteins, whatever. How real is that? What’s the best guess or is no guess needed? Is it ‘modified’ to better enable us to see what’s happening or is it like that, just that congested, just that open?

What’s the overall picture? Given the nature of it all I’d imagine thousands, maybe millions, of these processes never come to fruition, in this mad scramble, this ceaseless chaos. So what’s the scientific consensus on the state of it all? That a small minority of these processes succeeds or that the vast majority succeed and we rely heavily on ‘braking’ mechanisms to stop them? Is the human body in a sort of chemical equilibrium at all times…?

Those kind of things I’d love to see/hear and conveniently collected up hereabouts for me – I realize it’s all available out there somewhere in the chemistry textbooks but……

It is wonderful

I will have these animations playing on computer screens almost permanently in my home.

I’ll get wall posters showing stills….

🙂

Drew Berry
Posted 9 months ago

In reply to:

This is the greatest thing. I wonder if we could get more information as to the scientific accuracy of what is portrayed? The sizes and shapes of the molecules – are they all guaranteed 100% correct? If not when what are the tolerances, just what should we bear in mind when watching? The behaviour of the molecules most especially those astounding ‘walking’ things – how were they arrived at? We can take it as real that’s how they look and how they operate? Why/how do they operate like that? What causes a leg to swing forward and clamp on? And then why does it release? And the contents of the cell – all that amazing crowd of structures and proteins, whatever. How real is that? What’s the best guess or is no guess needed? Is it ‘modified’ to better enable us to see what’s happening or is it like that, just that congested, just that open? What’s the overall picture? Given the nature of it all I’d imagine thousands, maybe millions, of these processes never come to fruition, in this mad scramble, this ceaseless chaos. So what’s the scientific consensus on the state of it all? That a small minority of these processes succeeds or that the vast majority succeed and we rely heavily on ‘braking’ mechanisms to stop them? Is the human body in a sort of chemical equilibrium at all times…? Those kind of things I’d love to see/hear and conveniently collected up hereabouts for me – I realise it’s all available out there somewhere in the chemistry textbooks but…… It is wonderful I will have these animations playing on computer screens almost permanently in my home. I’ll get wall posters showing stills…. 🙂

arthur brogard

Hi Arthur,

Glad you like the animations and great questions!
The molecule models were obtained from Xray crystallography which determines the position of the atoms in each protein. I then created a surface representation of the exterior of each protein to use in the animation. Visit pdb.org to find out more about such data.

The walking molecules (Dynein and Kinesin) were modelled on multiple forms of data. The structures are an assembly of multiple PDB models and the way they move has been a very active area of research for a couple of decades. The leader in this field of molecular research is Dr Ron Vale at UCSF and his work was the primary influence on the development of that part of the animation. Visit his lab’s webpage here for more information about what we know about the structure and how the molecular motors move:
https://valelab.ucsf.edu

The molecular world inside the cell is vastly more crowded than I represented it. I made aesthetic and visual communication choices to limit the density and complexity to make this watchable to the audience. To get a better sense of the dense, crowded nature of the molecular world, I highly recommend (!) the work of Dr David Goodsell, his superb illustrations and specifically his illuminating books. His writing style is very accessible to the public and his images are mind blowing in the world they reveal with unrivalled scientific accuracy and detail:
David Goodsell’s illustrations
http://mgl.scripps.edu/people/goodsell/illustration/public
Goodsell’s books
http://www.amazon.com/The-Machinery-Life-David-Goodsell/dp/0387849246

Hope this helps answer some of your questions and also gives you much new material to explore and learn from.

Also visit my work homepage for more such animations at WEHI.TV by my small team.
http://www.wehi.tv

Drew


And now some of the links:

https://valelab.ucsf.edu

http://mgl.scripps.edu/people/goodsell/illustration/public

http://www.amazon.com/The-Machinery-Life-David-Goodsell/dp/0387849246

http://www.wehi.tv

http://www.biointeractive.org

http://www.molecularmovies.org

image

David Bolinsky: Visualizing the wonder of a living cell | Talk Video | TED.com

Excerpt: But these machines that power the inside of the cells are really quite amazing, and they really are the basis of all life because all of these machines interact with each other. They pass information to each other. They cause different things to happen inside the cell. And the cell will actually manufacture the parts that it needs on the fly, from information that’s brought from the nucleus by molecules that read the genes. No life, from the smallest life to everybody here, would be possible without these little micro-machines. In fact, it would really, in the absence of these machines, have made the attendance here, Chris, really quite sparse.

Excerpt: But it’s really quite amazing that these cells, these micro-machines, are aware enough of what the cell needs that they do their bidding. They work together. They make the cell do what it needs to do. And their working together helps our bodies — huge entities that they will never see — function properly. Enjoy the rest of the show. Thank you.

Don Johnson – November 2014

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3 responses to “Interesting People I Have Met: E. Michael Ostap, Ph.D.

  1. Thank you for your interest in my research. I was quite surprised and pleased to find my work highlighted on your blog. However, I must take this opportunity to point out that you may have misinterpreted my use of the word “Brilliant” in our short conversation. I don’t remember the details of our discussion, but I am sure my goal was to express the biological wonder of this motor as “Fantastic” or “Amazing,” and not “Brilliant” in terms of ideas or thought.

    It is important for me to stress that evolution is the best scientific explanation for the functional diversity of molecular motors. In fact, cytoskeletal motors are a wonderful example of evolutionary tuning to adapt to biological needs. To me, the process of evolution is beautiful in its simplicity and robust adaptability, and the concept of evolution is of the highest scientific merit.

    Best wishes.
    E. Michael Ostap, PhD
    University of Pennsylvania.

    • Thank you Dr. Ostap for your kind and reasoned reply. I am somewhat amazed to see your response since this blog is very much small potatoes in terms of distribution and readership – and you had no idea who you were talking to on the flight to Texas.

      First of all, I must apologize for my assumption that your use of the word “brilliant” was the same as mine … your use would more aptly fit the second definition as “very impressive or successful,” and I thank you for your clarification and I will update my post to reflect that the definition is mine and not yours.

      That said, in part based on my background of close to 40 years in software development of complex real-time and distributed systems, and a layman’s keen interest in the ‘machines’ of life lead me to side with the Intelligent Design view of the marvels of nature, and thus my choice of the definition of ‘brilliant’ that I used in my post. Should you be curious about the thinking and writings of this laymen, I invite you to click on CATEGORIES on the right side of this blog and select ‘Intelligent Design’. I don’t suggest however that we enter into any kind of debate – your time and energies are much more valuable in searching out ways in which the many fragilities of the human body can be discovered and treated.

      Again, I thank you for your response … I have perused the Perelman resources you provided me and have found them very fascination. Were I a bit younger, I would love to pursue a second career in the mysteries of life. However, I have no regrets in investing such a large part of my adult life in software development.

      Best regards,
      don johnson

  2. Pingback: if you have evidence of design then surely you should be able to tell us exactly what that evidence is and what the mechanisms are that are responsible? — A dialog with a commenter at NCSE | A Yearning for Publius

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