Tag Archives: crystallography

Outsmarting HIV with X-Ray Crystallography

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Dr, Alian Akram, Lorry I. Lokey Center for Life Science & Engineering, Technion.

Outsmarting HIV


It sound like modern warfare, and indeed, even when aiming to outsmart a killer virus on a scale of about 100 nanometers, the latest technology makes all the difference. One of the deep passions behind Dr. Alian Akram’s pioneering crystallographic work in the Technion is a desire to advance treatments for HIV, the causative agent of AIDS.



Scientists in Akram’s lab investigate the general principles of how aggressive virus lock into the genetic resources of a patient – and how to prevent them from doing this. “It is a MUST to learn about the critical interactions and the mechanisms of resistance,” says Akram. The team is taking a sharp look at pathogen-host interaction and how the HIV virus literally hijacks the machinery of the host cell in order to replicate itself, and how it escapes the immune system. “We are hoping to determine the structures of key interacting molecules and develop new intervening strategies and drugs that prevent their interaction. We also want to understand the mechanism of emergent resistance in the proteins of this virus.”



Current drugs for HIV bind viral proteins – and yet it continues to mutate and regenerate. Akram’s team is working on a protein discovered in 2004 – intrinsic immunity APOBEC3G. This protein attacks the genome of HIV and causes hypermutation that leads to an abortive replication cycle for HIV. However, HIV expresses a protein that destroys APOBEC, so the Akram’s group wants to understand this process better so that it can be blocked.
“Crystal structure of Pseudouridine synthase in complex with RNA solved by  Akram Alian. The structure reveals base-pair rearrangement as the key mechanism to rRNA substrate selectivity  (http://rnajournal.cshlp.org/content/16/6.cover-expansion)”

Outsmarting HIV with X-Ray Crystallography

1 Comment

Dr, Alian Akram, Lorry I. Lokey Center for Life Science & Engineering, Technion.

Outsmarting HIV


It sound like modern warfare, and indeed, even when aiming to outsmart a killer virus on a scale of about 100 nanometers, the latest technology makes all the difference. One of the deep passions behind Dr. Alian Akram’s pioneering crystallographic work in the Technion is a desire to advance treatments for HIV, the causative agent of AIDS.



Scientists in Akram’s lab investigate the general principles of how aggressive virus lock into the genetic resources of a patient – and how to prevent them from doing this. “It is a MUST to learn about the critical interactions and the mechanisms of resistance,” says Akram. The team is taking a sharp look at pathogen-host interaction and how the HIV virus literally hijacks the machinery of the host cell in order to replicate itself, and how it escapes the immune system. “We are hoping to determine the structures of key interacting molecules and develop new intervening strategies and drugs that prevent their interaction. We also want to understand the mechanism of emergent resistance in the proteins of this virus.”



Current drugs for HIV bind viral proteins – and yet it continues to mutate and regenerate. Akram’s team is working on a protein discovered in 2004 – intrinsic immunity APOBEC3G. This protein attacks the genome of HIV and causes hypermutation that leads to an abortive replication cycle for HIV. However, HIV expresses a protein that destroys APOBEC, so the Akram’s group wants to understand this process better so that it can be blocked.
“Crystal structure of Pseudouridine synthase in complex with RNA solved by  Akram Alian. The structure reveals base-pair rearrangement as the key mechanism to rRNA substrate selectivity  (http://rnajournal.cshlp.org/content/16/6.cover-expansion)”

Nobel Prize lecture in Chemistry, Stockholm.

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The Nobel Lecture in Chemistry, Stockholm University, December 8, 2011
Courtesy of the American Technion Society

At the official Nobel lecture, Professor Dan Shechtman spoke about his groundbreaking discovery of quasicrystals in 1982.  He first explained periodicity and four-fold symmetry and that it looks the same, even if it is rotated. From 1912-1982 all crystals were considered to be ordered and periodic. No one expected something new to be discovered.

Using electron diffraction patterns, Prof. Shechtman was able to observe five-fold symmetry.  On the screen he shared a page from his original laboratory log book dated April 8, 1982 that listed the experiments that he performed and his observations on that day. Several years later he was joined by Ilan Blech and other scientists and together their work, initially rejected, was published and finally accepted in the scientific community.

Professor Shechtman asked why this discovery did not happen before 1982 as some 100,000 crystals were studied for a period of 70 years.  He said that quasicrystals are abundant, not rare. Aluminum alone has hundreds. They are stable and very easy and inexpensive to make.

He shared the five factors that helped lead to the discovery and acceptance:

1. TEM – Transition Electron Microscope. The discovery could not be made with x-rays and required this powerful tool that enabled scientists to see things at the atomic level.

2. Professionalism

3. Tenacity

4. Belief in self as a scientist

5.Courage

Nobel Prize lecture in Chemistry, Stockholm.

Leave a comment

The Nobel Lecture in Chemistry, Stockholm University, December 8, 2011
Courtesy of the American Technion Society

At the official Nobel lecture, Professor Dan Shechtman spoke about his groundbreaking discovery of quasicrystals in 1982.  He first explained periodicity and four-fold symmetry and that it looks the same, even if it is rotated. From 1912-1982 all crystals were considered to be ordered and periodic. No one expected something new to be discovered.

Using electron diffraction patterns, Prof. Shechtman was able to observe five-fold symmetry.  On the screen he shared a page from his original laboratory log book dated April 8, 1982 that listed the experiments that he performed and his observations on that day. Several years later he was joined by Ilan Blech and other scientists and together their work, initially rejected, was published and finally accepted in the scientific community.

Professor Shechtman asked why this discovery did not happen before 1982 as some 100,000 crystals were studied for a period of 70 years.  He said that quasicrystals are abundant, not rare. Aluminum alone has hundreds. They are stable and very easy and inexpensive to make.

He shared the five factors that helped lead to the discovery and acceptance:

1. TEM – Transition Electron Microscope. The discovery could not be made with x-rays and required this powerful tool that enabled scientists to see things at the atomic level.

2. Professionalism

3. Tenacity

4. Belief in self as a scientist

5.Courage