HTTP/1.1 200 OK
Date: Sun, 12 Feb 2012 18:49:54 GMT
Server: Apache/2.2.21 (Ubuntu)
X-Powered-By: PHP/5.3.9
Connection: close
Content-Type: text/html


<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Transitional//EN" 
  "http://www.w3.org/TR/xhtml1/DTD/xhtml1-transitional.dtd">

<html lang="en" xmlns="http://www.w3.org/1999/xhtml">
   <head>
      <meta http-equiv="content-type" content="text/html;charset=iso-8859-1" />
      <title>SDSU &raquo; Chemistry &amp; Biochemistry &raquo; Aileen F. Knowles: Mentors</title>
      <meta http-equiv="content-type" content="text/html;charset=iso-8859-1" />
      <meta name="keywords" content="chemistry,biochemistry,SDSU,San Diego State University, Aileen F. Knowles: Mentors " />
      <meta name="description" content="The Department of Chemistry and Biochemistry at San Diego State University" />
      <meta name="robots" content="index,follow" />
      <meta name="copyright" content="Copyright &#169; 1998-2012 San Diego State University" /> 
      <link rel="icon" href="http://www.chemistry.sdsu.edu/favicon.ico" type="image/x-icon" />
      <link rel="shortcut icon" href="http://www.chemistry.sdsu.edu/favicon.ico" type="image/x-icon" />

      <link href="/style/template.css" type="text/css" rel="stylesheet" media="all" />
      <link href="/style/menu2.css" type="text/css" rel="stylesheet" media="all" /> 
   </head>
<body>
   <div id="centercontent">
   <div class="hotlinks">
<form method="get" action="http://google.calstate.edu/search" name="search_form">
<ul>
   <li> <a href="http://www.sdsu.edu/">SDSU</a></li>
   <li>| <a href="/">Dept home</a></li>
   <li>| <a href="/donate/">Donate</a></li>
   <li>| <a href="/sitemap.html">Sitemap</a></li>
   <li>| <a href="/welcome/contact.php">Contact</a></li>
   <li>| 
    <input name="access" value="p" type="hidden">
    <input name="site" value="sdsu" type="hidden"> <!-- collection -->
    <input name="client" value="sdsu-edu" type="hidden"> <!-- front-end -->
    <input name="proxystylesheet" value="sdsu-edu" type="hidden"> <!-- front-end -->
    <input name="oe" value="UTF-8" type="hidden">

    <input name="output" value="xml_no_dtd" type="hidden">
    <input name="sort" value="date%3AD%3AL%3Ad1" type="hidden">
    <label for="q">Search SDSU</label> 
    <input id="search" name="q" size="24" maxlength="255" value="" alt="Search San Diego State University" type="text">
    <a href="javascript:document.search_form.submit()" onMouseOver="window.status='Search Our Site'; return true;">GO&raquo;</a>
<input type="hidden" name="hl" value="en" /> <input type="hidden" name="lr" value="" /> <input type="hidden" name="ie" value="ISO-8859-1" />
</li>
</ul>
</form>
   </div>
      <div id="generic-header-small" class="header-small">
	 <a href="http://www.sdsu.edu"><img src="/style/images/SDSU_3ColorRevOnRedSmall.gif" alt="San Diego State University" height="80" width="107" border="0" /></a>
	 <div class="header-type">
	    <h1>Chemistry and Biochemistry</h1>
	 </div>
      </div>

      <div id="topnav">  
	<div style="width:100%; background:#d2c694; text-align:center;">

<div class="menu" style="text-align:left;">
<ul>
<li><a href="/welcome/">Visitors<!--[if IE 7]><!--></a><!--<![endif]-->
<!--[if lte IE 6]><table><tr><td><![endif]-->

	<ul>
	<li><a href="/news/">News</a></li>
	<li><a href="/welcome/" class="drop">Welcome<!--[if IE 7]><!--></a><!--<![endif]-->

<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul>
        <li><a href="/welcome/" class="daddy">Program&nbsp;Summary</a></li>
        <li><a href="/welcome/SanDiego.php" class="daddy">San Diego</a></li>
		</ul>
<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>

	<li><a href="/directory.php" class="drop">Directory<!--[if IE 7]><!--></a><!--<![endif]-->
<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul>
			<li><a href="/directory.php">General</a></li>
			<li><a href="/faculty/">Faculty</a></li>
			<li><a href="/staff.php">Staff</a></li>

		</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>
         <li><a href="/alumni/" class="daddy">Alumni</a></li>
         <li><a href="/jobs/jobform1.php" class="daddy">Employers</a></li>
         <li><a href="/facilities/" class="daddy">Facilities</a></li>
         <li><a href="/welcome/contact.php" class="daddy">Directions</a></li>
         <li><a href="/news/calendar.php" class="daddy">Calendar</a></li>
         <li><a href="/sitemap.html" class="daddy">Site Map</a></li>
	</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
</li>
<li><a href="/undergrad/">Undergraduates<!--[if IE 7]><!--></a><!--<![endif]-->
<!--[if lte IE 6]><table><tr><td><![endif]-->
	<ul>
         <li><a href="/degrees.php">Degrees</a></li>
         <li><a href="/courses/">Courses</a></li>
         <li><a href="/research/ugrsrch.php" class="drop">Research<!--[if IE 7]><!--></a><!--<![endif]-->
<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul>
               <li><a href="/research/ugrsrch.php#Courses">course&nbsp;credit</a></li>
               <li><a href="/research/ugrsrch.php#Projects">projects</a></li>
               <li><a href="/research/ugfellowships.php">fellowships</a></li>
               <li><a href="/research/testimonial.php">testimonial</a></li>
		</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>
         <li><a href="/SAACS/">SAACS</a></li>
         <li><a href="/jobs/">Jobs</a></li>
         <li><a href="/forms/">Forms/Handouts</a></li>
	</ul>
<!--[if lte IE 6]></td></tr></table></a><![endif]-->
</li>
<li><a href="/graduate/">Graduate&nbsp;Study<!--[if IE 7]><!--></a><!--<![endif]-->
<!--[if lte IE 6]><table><tr><td><![endif]-->
	<ul>
         <li><a href="/degrees.php#GradAdmission">Admissions</a></li>
         <li><a href="/degrees.php#Graduate">Degrees</a></li>
         <li><a href="/courses/">Courses</a></li>
         <li><a href="/forms/">Forms/Handouts</a></li>
         <li><a href="/seminars/gradseminars.php">Graduate&nbsp;Seminars</a></li>
         <li><a href="/CGSA">Chem Grad Student Assn</a></li>
         <li><a href="/seminars/jc_seminars.php">Journal&nbsp;Club</a></li>
         <li><a href="/jobs/">Jobs</a></li>
	</ul>
<!--[if lte IE 6]></td></tr></table></a><![endif]-->
</li>

<li><a href="/research/">Faculty/Research<!--[if IE 7]><!--></a><!--<![endif]-->

<!--[if lte IE 6]><table><tr><td><![endif]-->
	<ul>
         <li><a href="/faculty/">Faculty&nbsp;directory</a></li>
         <li><a href="/facilities/">Facilities</a></li>

	<li><a href="/research/" class="drop">Research&nbsp;Areas<!--[if IE 7]><!--></a><!--<![endif]-->

<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul class="left">
               <li><a href="/research/analytical.php">Analytical</a></li>
               <li><a href="/research/biochem.php">Biochemistry</a></li>
               <li><a href="/research/inorganic.php">Inorganic</a></li>
               <li><a href="/research/organic.php">Organic</a></li>
               <li><a href="/research/organomet.php">Organometallic</a></li>
               <li><a href="/research/physical.php">Physical</a></li>
		</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>
    
	<li><a href="/research/ugrsrch.php" class="drop">Undergraduate Research<!--[if IE 7]><!--></a><!--<![endif]-->

<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul class="left">
               <li><a href="/research/testimonial.php">testimonial</a></li>
               <li><a href="/research/ugrsrch.php#Courses">course&nbsp;credit</a></li>
               <li><a href="/research/ugrsrch.php#Projects">projects</a></li>
               <li><a href="/research/ugfellowships.php">fellowships</a></li>
		</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>
    
	<li><a href="/seminars/seminars.php" class="drop">Seminars<!--[if IE 7]><!--></a><!--<![endif]-->

<!--[if lte IE 6]><table><tr><td><![endif]-->
		<ul class="left">
               <li><a href="/seminars/seminars.php">Department</a></li>
               <li><a href="/seminars/gradseminars.php">Graduate</a></li>
               <li><a href="/seminars/jc_seminars.php">Journal&nbsp;Club</a></li>
               <li><a href="/seminars/facseminars.php">Faculty</a></li>
		</ul>

<!--[if lte IE 6]></td></tr></table></a><![endif]-->
	</li>
         <li><a href="/research/resources.php">Resources</a></li>
         <li><a href="/deptfiles/">Internal&nbsp;Links</a></li>
         <li><a href="/news/calendar.php">Calendar</a></li>

	</ul>
<!--[if lte IE 6]></td></tr></table></a><![endif]-->
</li>
</ul>
</div> <!-- end menu -->
</div> <!-- end wrapper -->

<br style="clear:both" />
      </div>
      <div class="col-full-2nd-level">

<br />

<h3>My Mentors</h3>

<p>
I've been extremely lucky in having the
opportunities to work with brilliant people who have shaped an entire research
field.  Here are my personal remembrances and tributes to my mentors.<p>
</p>

<p>
My thesis advisor is Professor Anthony Norman of
the University of California at Riverside. Tony was fresh out of the University
of Wisconsin when he came to UCR and was interested in the mechanism of action
of vitamin D. Tony just succeeded in the synthesis of radioactive vitamin D,
which meant that the path of vitamin D could be followed in an animal receiving
physiological, rather than pharmacological, doses of the vitamin. Tony
suggested that I determine the target tissue of tritiated vitamin D in ricketic
chickens. I was foolish enough to think of the project as being too
physiological, and went off to a project totally unrelated to vitamin D!  My
thesis research, which was concerned with deoxyribonucleotide synthesis, still
involved scraping yards of chicken guts-the source of fast growing mucosa
cells, and earned me a membership in the prestigious "One-Mile Club" (there is
also a "Five-Mile Club"). Tony's research is responsible for defining the role
of vitamin D-derived 1,25-dihydroxycholecalciferol as a hormone and is the
founder of the field. He is still busy with research, organizing meetings, and
publishing books.
</p>
<p>
In his first year as a faculty at UCR, Tony
taught a graduate course on oxidative phosphorylation while commuting between
UCR and UCLA discovering phosphohistidine with Paul Boyer. One of the readings
he assigned for the course was "Mechansims in Bioenergetics" by Efraim Racker. Ef's
enthusiasm for bioenegetics was so palpable and infectious that I decided to
write to him, among others, for a post-doctoral position. Maybe the fact that
Tony had worked with Boyer had something to do with Ef's decision to accept me
into his lab. When I showed some hesitation about leaving California and told
Tony that I was waiting to hear from other labs on the West coast, Tony told me
that I should jump at the opportunity because Ef was a "big fish."  So off I
went to the East coast, a decision that set the course of my scientific career.</p>
<p>
I worked with Ef for seven years at Cornell,
from 1968-1970 and 1972-1977. This was considered too long for a post-doc by
the standard of by-gone days, but I would not have traded the experiences for
anything else. Ef was the most brilliant man that I've ever met and I felt
privileged to be part of his group at the peak of his career. Ef's life was
recounted in an article by Jeff Schatz: "Efraim Racker: 28 June 1913 to 9
September 1991" (Comprehensive Biochemistry, 40, 253-276). Ef had about 20 post-doc
fellows from different parts of the world at any one time, and I'm sure each of
us remembers him in a different way. In retrospect, it was amazing that there
was little disharmony in his very large group partly because each of us had our
own projects. Ef was demanding of us, but no more than of himself. His office
door was always open and he had his own bench area in the lab, which was next
to mine from 1972-1977. I witnessed the famous experiment (Racker and Stoeckenius,
JBC, 249, 662-663 (1974)) that demonstrated ATP synthesis driven by proton
gradient, using vesicles reconstituted of bacteriorhodopsin and mitochondrial F<sub>o</sub>F<sub>1,
</sub>thus resolving a long-standing controversy. The experiment was performed
by Ef himself using an ordinary pH meter in a single afternoon, while Dr. Stoeckenius
looked on. The simple beauty of the experiment has never ceased to awe me. </p>

<p>
My first project at Cornell was the resolution
of a coupling factor of beef heart mitochondria. This was shortly after OSCP (oligomycin
sensitivity conferring protein) was isolated. My first year ended in total
failure, however, I did manage to tear F<sub>6</sub> away from F<sub>1</sub> in
the 2<sup>nd</sup> year. I'm quite proud of the fact that while several other
coupling factors have fallen by the wayside, F<sub>6</sub> has been proven to
be an integral part of FoF<sub>1</sub>. It was a great pleasure for me to see
that the three-dimensional structures of both OSCP and F6 were resolved
recently. </p>

<p>
My project during my second stay in Ef's lab was
reconstitution of the Ca pump of sarcoplasmic reticulum. Yasuo Kagawa had
developed the technique of proteoliposome reconstitution and it was being
applied to the reconstitution of oxidative phosphorylation with isolated
mitochondrial components. Ef then expanded this research to the different
ATP-driven membrane transporters. Ef's fame spread far and wide, and many
scientific luminaries visited his lab in spite of the fact that Ithaca was an
out of the way small town in upstate New York. I remember Peter Mitchell
sitting in on our lab meeting, and working with Gobind Khorana on an idea of
his, which resulted in a JBC paper. In addition to these dignitaries, my lab
life was enlivened by the many talented and colorful fellow post-docs who went
on to have their own illustrious careers: Don Schneider, Carol Cunningham,
Maurice Montal, Bernie Trumpower, Charlie Yocum, Dennis Lang, Chris Miller, Gera
Eytan, Nathan Nelson, Baruch Kanner, Ramon Serrano, Bill Dubinsky, Ed LaBelle, Piotr
Zimniak, Judy Belt, and Marcelo and Ramona Alfonso. We were all, at one time or
another, taken under the wings of Anne (Kandrach) Ghiorse, Ef's right-hand
woman. Sadly, Anne passed away a few years ago. </p>

<p>
It was also at Cornell that I met Leon Heppel
(see a "Reflections" article in JBC about Leon by Maxine Singer, JBC 278,
47351-47356 (2003)). I remember him coming back from his sabbatical in London
being very excited about his finding that extracellular ATP caused permeability
change in transformed cells. I could not have predicted that, years later, I
would be devoting considerable efforts on the enzymes that are involved in
terminating purinergic signaling, the ecto-ATPases.
</p>

<p>
My other mentor is Harvey Penefsky. Harvey and
Maynard Pullman isolated the mitochondrial ATPase, F<sub>1</sub>, while working
with Ef. Unraveling the mystery of F<sub>1</sub> became Harvey's lifetime work.
It was in his lab at the New York Public Health Research Institute (1970-1972)
that I resolved the 5 subunits of beef heart F<sub>1</sub>. It was another
piece of research that brought great satisfaction. I have sometimes wondered
how my career would have turned out if I had not left the field of F<sub>1</sub>.
</p>

<p>
In spite of his influence and respect accorded
him by other F<sub>1</sub> researchers, Harvey has always been a modest man.
One could not have asked for a better boss, who was understanding and patient.
I never felt pressured in getting my work done even though Senior and Brooks
were going after the same prize, which I didn't find out until later. Harvey is
a hands-on person and is a genius in devising and constructing analytical
apparatuses, which allowed him to address mechanistic questions that would not
have been possible otherwise. From Harvey, I learned that it is possible to do great
science without a large group. But of course, one would need to have Harvey's
intellect to pull it off. In 1994, I enjoyed Harvey and Zia's hospitality again
in his lab at the SUNY Health Science Center in Syracuse. I had the opportunity
to learn of all the progress and controversies in F<sub>1</sub> research and I
was extremely pleased that I was able to write another Knowles and Penefsky
paper. 
</p>

<p>
After Cornell in 1977, I spent several years
working at UCSD as an independent research scientist in the lab of another
great biochemist, Nathan Kaplan. In spite of his manners of absent-mindedness, Nate
was a major moving force behind many great endeavors in biochemistry. Besides
his work on pyridine nucleotide-linked enzymes, Nate was best known for
launching "Methods in Enzymology" with Colowick. Nate's influence and extensive
network in the scientific community was obvious in a memorable symposium that
he organized to pay tribute to Martin Kamen. I had never seen so many Nobel
Prize laureates and famous scientists at one gathering than on that occasion.
</p>

<p>
When I arrived at UCSD, Nate and
Gordon Sato just received an NIH grant to establish a nude mouse colony for
cancer research. I was again thrust into a large and bustling group of colorful
and fun-loving people who were also doing first-rate research. In the early
1980's, Nate was enthusiastically talking about the first biotech company in
San Diego, Hybritech. But even Nate could not have foreseen the astounding
growth of the biotech industry in San Diego in the ensuing two decades. He
would have been proud of the fact that several of his students have since
founded their own successful companies. 
</p>

<p>
The culture of academic life has
changed considerably since my days of apprenticeship. I feel nostalgia for
those days for many reasons and I treasure the friendship and camaraderie of my
colleagues. Most of all, I'm grateful to all my mentors for showing me the
enjoyment of doing science.</p>

<p>
-- Aileen F. Knowles
</p>

<HR>

<P ALIGN=CENTER><FONT SIZE="2">[ <A
HREF="http://www.chemistry.sdsu.edu/chemistry/index.php">Chem & Biochem Home</A>
| <A HREF="http://www.chemistry.sdsu.edu/chemistry/undergrad.php">Undergraduate</A>
| <A HREF="http://www.chemistry.sdsu.edu/chemistry/graduate/">Graduate</A>
| <A HREF="http://www.chemistry.sdsu.edu/chemistry/research/">Research</A>
]<BR>
<EM><A HREF="/degrees.php#GradAdmission">SDSU Chemistry & Biochemistry Graduate Admissions</A></EM><BR>
</FONT> 
<FONT SIZE="1">
<!--
SDSU Chem pages originally designed by Cheryl and 
 <a href="http://webpub.allegheny.edu/employee/d/dburkey/">David Burkey</a>.<br>
-->
Web minion: <a href="mailto:acooksy@sciences.sdsu.edu">A.L. Cooksy</a>.
Last modified: August 24 2010 15:46:45.</FONT><BR><BR>
<A HREF="http://www.sdsu.edu/index.html"><IMG ALIGN="MIDDLE"
SRC="http://www.chemistry.sdsu.edu/chemistry/graphics/SDSUhome.gif"
BORDER="0" WIDTH="300" HEIGHT="22" ALT="SDSU HOME"></A></P>
</BODY>
</HTML>


