Ira mellman lectures meaning

This is where I hold people's feet to the fire: is this really the most important thing you can think of spending your time on? If so, why? Tell me why this gets you excited? I've had just wonderful mentors, starting with my undergraduate mentor David Miller [at Oberlin]. I went to Rockefeller for a post-doc. My department head was a brilliant man called Zanvil Cohn , who did excellent immunology and cell biology on macrophages.

He was a member of the National Academy of Sciences and all of that, but was a very self-effacing, quiet and humble man. He taught me a lot about project selection: if you've chosen the biology correctly, the rest will take care of itself. I also learned from him that the best mentors act as logic filters. Much of the work I did during my post-doc at Rockefeller was with Ralph Steinman.

Ralph was one of the younger faculty and was embroiled in probably the most important piece of work I've ever seen up close, which was the discovery and characterization of dendritic cells.

Ira mellman lectures meaning

This work eventually won him a Nobel Prize. I could see him [Steinman] struggling with something new. He was also brash and opinionated, and his life was made difficult by all of these factors. But these problems were counterbalanced by the fact that he was doing something that was clearly of such importance; it entirely changed the field of immunology.

Dendritic cells link innate and adaptive immunity, and he discovered how this happens. Ralph showed how antigen presenting dendritic cells could detect these innate immune molecules [via TLRs], which was the missing connection for over years. Ilya Metchnikov got the Nobel Prize for essentially describing macrophages and innate immunity, while Paul Ehrlich got the prize the same year for discovering humoral immunity.

They thought they were working on two separate immunological processes, but Ralph was finally able to connect these two areas. By detecting innate signals to initiate adaptive immunity, perhaps the most important central function of dendritic cells must be the presentation of antigens to T cells. It was this realization that set me off trying to understand how these cells accomplish this feat, and do it better than almost any other cell we know of.

So, I was cast in the direction of marrying the fields of immunology and cell biology. I have long felt that there is a large gulf between the fields of immunology and cell biology. Metchnikov is a point of connection because his work on macrophages led to the discovery of endocytosis, intracellular degradation and lysosomes. But from that point, the fields really diverged.

Cells are viewed as functional units that must be understood in the context of a complex system. On the other hand, cell biologists lose interest in problems as a function of the square of the number of cells involved. They view an immune system with millions of cells engaging in complex interactions as hopelessly abstruse. Understanding the mechanistic [cell biological] basis by which complex systems work is probably one of the greatest challenges that that exists.

Neuroscientists do this better than almost anybody else but [the brain] is such a complex system. In immunology there is enormous opportunity for mechanistic biology to help human health. The immune system is probably the best site for therapeutic intervention that we have—you can literally take it out of an organism, modify it and put it back.

The part of immunology that has fascinated me the most is its relationship to cancer. I had some dear friends, family members, lab members, and colleagues who were diagnosed with, and eventually succumbed to cancer—Ralph Steinman was diagnosed with pancreatic cancer around the time I decided to move to Genentech. When I discussed this move with him, I thought he would say that going to a company would be a terrible idea and an abandonment of science.

So I joined Genentech, and remain here today. As usual, Ralph was correct. What set of research questions or projects has you most excited about coming into lab today? Speaker: Ira Mellman. Audience: Educators of H. Talk Overview Dr. Leave a Reply Cancel reply Your email address will not be published. For Educators New! To find out more see our Privacy Policy.

So here you have this nice example of the innate system Now antibodies are not made by Antibodies instead B lymphocytes exist in great number found throughout What that's again a manifestation of, The lymph drains into the lymphatics, So these B-cells So here you see a clone of B-cells that gives rise Now it turns out that things are not that simple, What I've just shown you in that video isn't in every sense correct, This complex of the We've been talking about CD-4 T-cells, CD8 T-cells express exactly the same type of T-cell receptors, Now CD8 restricted T-cells In much the same way, The CD8 system and the class I system That type of endogenous pathogen, Now the way These granules line up at the interface, or synapse, All leading to its rapid death.

So in other words, the virus has In fact over the last several In the absence of genes that are required T-cells become activated The T-cell receptor itself is a signaling molecule, Further, selected cells in the immune system Only the dendritic cell can wake If you delete dendritic cells from a mouse using a variety Because only Now the other side of the coin here though Dendritic cells play also a key role Now probably though the most important Again, by virtue of the fact that they express So then as I'm mentioning in words, It took almost 80 to years later to really figure this out, Now the basic logic of The idea is as follows, dendritic cells exist Here we are looking at the skin, at the epidermis, Indeed, the fact that these dendritic cells Immature dendritic cells are shown here What you can see is that all the MHC molecules, In addition they don't express co-stimulatory So we view these This flip from the immature to the mature state Were it not for that fact, not for the fact that So it's actually Now as cell biologists interested in membrane traffic So here on the left you are looking at a diagram At the same time, As long If the invariant chain is removed, the class II molecule can This happens for a variety of reasons, In fact the lysosomes are activated Normally The reason for that has been described As a consequence of maturation, Now this is a diagram just quickly as to how this works.

Maturation reduces Now the molecules Here is a video taken by Amy Chow So as I've mentioned earlier, Now what you can see This is a video in which we are just able to visualize Again, this is probably, Our conventional view of Proteins, antigens, whatever microbes are collected, So we had not really anticipated So the normal But uptake So why is it that class II molecules do not enter in the mature cell?

Over the last several We know from the work of Scott Ember and others Now this happens in dendritic cells because if you look actually Ubiquitin is a small When Jeoung-Sook Shin And, indeed, not only So here you are looking So the bottom line is that in Dendritic cells shown here in red So the best example I can give you Those proteins are going to be degraded Remember I told you that only dendritic cells And I also just told you that the predominate cell, How do we guard ourselves against So how do They deal with it by having developed It was really first described Here it was thought to be the case