Dean's Newsletter
Archive of previous newsletters
Cajal Club Explorer Award
October 11, 2006
A couple of weeks ago, Gary Paige, MD, PhD, Chair of the Department of Neurobiology and Anatomy, informed me that Ania Majewska, Ph.D., an Assistant Professor who had recently joined his Department, had won the Cajal Club Explorer Award. Receiving such a prestigious award is a cause for recognition and celebration. What make's this all the more special, however, is Ania's personal and professional story.
The Cajal Club
Let me begin with a sketch of the Cajal Society and a summary of Dr. Majewska's work. Most of this information comes from Ania herself, so these are largely her words.
Ramon y Cajal is often considered to be the grandfather of neuroscience. Working at the turn of the 20th century in Spain, his interest in the relationship between structure and function in the nervous system was aided not only by his training as a physician, but also by his gift as an artist. Using the Golgi technique of delineating single nerve cells, he spent countless hours at his light microscope, which he acquired using his life savings, trying to understand how the structures he observed in his fixed specimens behaved in the live tissue.
Based on his observations of static images, Cajal arrived at a number of postulates of nervous system function that remain the cornerstones of neuroscience today. His three main contributions were: 1) the neuron doctrine – which convinced the neuroscience community that the nervous system was made up of individual cells; 2) the law of dynamic polarization – which states that nerve cells receive information on their cell bodies and dendrites, and conduct information to distant locations through axons; and 3) the law of synaptic specificity -- which postulates that nerve cells communicate through specialized structures that connect neurons into highly specific networks. All three of these postulates have withstood the test of time and are a testament to Ramon y Cajal's amazing insight into the workings of the nervous system.
The Cajal Club is the oldest ongoing neuroscience professional society and was founded on April 3, 1947 at a meeting of the American Association of Anatomists. The founding members were notable neuroanatomists of their day, and the society has now grown to over 500 members throughout the world. Since its inception, the Cajal Club has met once a year to promote scientific and social interactions between neuroanatomists. In May 2001, the Cajal Club held a three-day meeting at the Cajal Institute in Madrid, Spain. This meeting was the first time the club met outside North America. A book based on the proceedings of this meeting, notably titled "Changing Views of Cajal's Neuron," was published to commemorate the 150th anniversary of Cajal's birth.
Each year the Cajal Club gives out three prizes to outstanding neuroscientists at different stages of their careers. This year's Cortical Explorer prize, which honors a junior scientist who received their advanced professional degree within the last 6 years, was awarded to Dr. Majewska. The award includes an inscribed certificate, a cash prize and support for travel to this year's Cajal Club meeting. Ania joins Apostolos Georgopoulos, who received the 2006 Cortical Discoverer Award for senior scientists and Bradley Molyneaux, who received the Scholar Award for student scientists. Previous winners of the Cortical Discoverer Award include illustrious neuroscientists such as Gyorgy Buzsaki, Irving T. Diamond, Charles D. Gilbert, Patricia S. Goldman-Rakic, Jon Kaas, Pasko Rakic and Wolf Singer, to name just a few.
Dr. Majewska's research
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Assistant Professor Neurobiology and Anatomy |
Dr. Majewska uses state-of-the-art technology, an approach she shares with her physicist husband, Dr. Edward Brown, and recapitulates Cajal's fundamental strategy of trying to understand neural function by observing structures in live tissue. In contrast to Cajal's focus on understanding the nervous system function as a whole, based on the structures he observed in fixed specimens, Dr. Majewska's research is aimed at understanding how single-cell structure changes dynamically over time to influence nervous system function. Cajal had available only a traditional light microscope that did not permit the examination of live tissue. Dr. Majewska has the benefit of a powerful novel optical technology called the two-photon microscope, which allows the imaging of the live brain in real time with tremendous resolution. This has allowed her to study the tiny compartments, called dendritic spines, that connect neurons in the cerebral cortex, teasing out how their structure influences the function of the synapse and networks of neurons. Dendritic spines are very small (<1um diameter) spheres that are connected to the dendrite of a cell by a very thin stalk. Cajal was the first to describe these structures. At a time when his contemporaries where dismissing them as artifacts of the staining procedure, he postulated that these were the points of contacts between cells (synapses) and that their structure related to learning. We now know that over 95% of excitatory synapses in the central nervous system are made onto dendritic spines. But because of their incredibly small size, 100 years after Cajal's postulate, we still know very little about how the shape of the dendritic spine, and changes in that shape, are related to cellular and behavioral learning.
Beginning with her PhD thesis (Columbia, '01, Laboratory Director: Rafael Yuste), Dr. Majewska has been studying how dendritic spine morphology affects communication between neurons. Her PhD thesis explored the mechanisms of calcium signaling at dendritic spines in live brain tissue slices. Calcium is one of the most important messengers for implementing changes in synaptic strength, and these changes are widely believed to be the cellular correlates of learning and memory. At the time of her doctoral work, however, very little was known about how calcium was regulated in the live dendritic spine. Using two-photon microscopy, she was able to image changes in calcium concentration at single dendritic spines after eliciting electrical activity in the cell. Her work showed that the shape of the spine and its connection to the dendrite influenced the size and duration of the calcium transient at the synapse. Surprisingly, she also discovered that spine shape was not static but was constantly changing and that this influenced the calcium transient – suggesting that changes in spine shape can alter the learning paradigms at single synapses.
To learn whether changes in spine shape relate to changes in brain function, Dr. Majewska completed post-doctoral work with Mriganka Sur at MIT where she studied how vision influenced the morphology of the dendritic spine, again using two-photon microscopy to peer at tiny synapses hard at work in the intact brain. Ania's work showed that depriving animals of vision made the dendritic spines in the visual part of the brain more dynamic – they showed more pronounced changes in their shape. Her data suggested a model whereby a lack of visual stimulus causes less calcium influx at the spine and leads to increased changes in spine shape. This in turn further alters the calcium transient and ultimately leads to a dismantling of the synapse and a loss of the spine structure.
Here in Rochester, Dr. Majewska and her team are examining whether her model of the progression of dendritic spine changes is true at all synapses in visual cortex and are exploring the mechanisms for changes in spine shape at the molecular level. The Majewska lab is becoming more translational, exploring the progression and dynamics of spine shape in neurodevelopmental disorders such as Rett syndrome, Fragile X syndrome and Fetal Alcohol syndrome. She hopes that by understanding the dynamics and mechanisms of spine shape changes in animal models of these disorders, as well as during normal development, we will gain insight into possible targets for therapeutic treatment.
Dr. Majewska's work has won accolades from fellow scientists working in related fields. Dr. David Pinto, Assistant Professor of Biomedical Engineering, states that Ania's "methodologic approaches are now being used by many other labs; in addressing the question of how learning takes place in the brain, she has "opened up a whole new field that explores the neural mechanics of learning." Dr. Maiken Needergaard, who also works with the 2-photon microscope comments that Ania is a "brilliant young woman whose new approach to structure-function in the brain has great promise. As a superb scientist who is balancing professional and family life, she fits perfectly in the Rochester environment and culture."
Dr. Majewska: From Poland to Rochester
Born in Warsaw, Poland, Ania and her family moved to Kuwait when she was 6. She spent her formative years living in both the Middle East and Poland, attending an international English-speaking school in Kuwait and spending her summer vacations in the Polish countryside. According to Ania, the diversity and affluence of Kuwaiti society afforded her many wonderful opportunities as a child – she had friends from all over the world, traveled extensively, was exposed to wonderful teachers and always had her afternoons packed with extracurricular activities. Her mother told her that as a child she was very social but not at all interested in academics. Her brother (currently a professor of human genetics at McGill) was always the family genius.
Ania had just finished her O level examinations and had two more years of high school left, when her well-organized life was thrown into disarray by the Iraqi invasion of Kuwait. She was in Poland taking her Polish exams when her parents were evacuated two weeks after Iraq invaded. They came home with only two suitcases from their entire 10-year Kuwaiti experience. Ania was amazed at what they packed – the negatives of all photographs, Ania's ballet clothes, and all of the trophies that her brother and she had received as children.
Needless to say, this was an extremely difficult time for the Majewska family as a whole. For Ania, adjusting to her Polish school was difficult. She buried herself in her classes and developed a particular rapport with her chemistry teacher, who cultivated her interest in organic chemistry. In the meantime, even though she had not finished high school, she started applying to American universities in the hope that her O levels would suffice to gain admission. Ania was 16 years old and her parents did not want her to go abroad, but agreed that she could attend one of three places where her family had friends. So, Ania said matter-of-factly, "I was thrilled when I got into Stanford University, and I couldn't wait to start." At Stanford she majored in Chemistry but added Biology for a double major and started research in Alzheimer's disease at a laboratory in the medical school. That work culminated in an honors thesis and led to her life-long interest in understanding the brain.
Dr. Majewska developed a specific interest in synaptic plasticity for her graduate work and studied with Rafael Yuste at Columbia University for her PhD research. The remainder of this story, which includes science, marriage, children and two additional moves, are best told by Ania directly:
"At Columbia 'Rafa' was a young faculty member interested in using two-photon microscopy to understand how synapses worked in intact brain tissue. The project was challenging both in terms of the technology (my first project was to build the microscope) and also the biology of quantitating calcium changes in these tiny synaptic compartments. I found the work challenging, often frustrating, but ultimately fascinating. It was in Rafa's lab and thanks to his encouragement and mentorship that I realized that research was going to be my life. I owe him a huge scientific debt but also a personal one. He dragged me into lab on Sunday morning (after a very late night out with my friends) to meet a physicist who worked on the technique of two-photon microscopy. I was furious right up until we were introduced. That was how I met Edward Brown. Our scientific and personal journeys continued together from that point. I graduated and moved to Boston where Edward was doing his post-doc. Mriganka Sur's lab at MIT gave me the freedom and opportunity to develop new techniques for studying dendritic spines in the intact animal and understanding changes at synapses in the context of the neural networks that interact with our environment. Thanks to my broad research experience in Mriganka's lab, and his excellent mentorship, I further developed my scientific interests and I feel that I became very well equipped to start my own lab. Edward and I found ourselves on the job market. It was not easy finding two academic positions that provided good environments for both our research programs and were within a reasonable commuting distance. After an intense period of interviews we accepted offers at the University of Rochester. Because of its breadth and excellence in research, the U of R was able to provide environments that appealed to both of us, all within the same university. The department of Neurobiology and Anatomy is an excellent fit for my research, and the department of Biomedical Engineering is a great place for Edward to develop his tumor imaging program. The diverse neuroscience society, clinical enterprise and the concentration in optics research benefits both of our research endeavors, and the open, collaborative environment drew us in even at the interview stage. Additionally, the University of Rochester did not view our two-body problem as a nuisance but as an opportunity. The two departments were flexible and coordinated, ensuring that the joint recruitment proceeded smoothly, providing us with simultaneous excellent offers that were hard to turn down. We have been here for a year now and we haven't once regretted our decision to come. Both of our laboratories are up and running, and we are starting to see preliminary results which are immensely satisfying. We have both set up interesting collaborations and are embarking on a joint project soon. We run our independent laboratories in close proximity and our lab members interact frequently. We really appreciate our beautiful house on 7 acres in Honeoye Falls (for the price of a one bedroom apartment in Boston) and love to see our 15-month-old son, Robert, run around in the yard."
The detail missing from Ania's history of her recruitment to Rochester is the rather unusual manner in which it took place. It all started with an unsolicited email from Ania to Dr. Paige! A lengthy phone call from Gary revealed that her husband, Ed Brown, had an offer from Cornell (Ithaca), and that she was looking for a reasonable fit nearby. Dr. Rick Waugh, Chair of Biomedical Engineering had known that Ed was looking at Cornell, as there were communications from the BME Department there seeking a solution for Ania. While potentially sensitive, Dr. Paige called the Chair at Cornell to express an interest in matching both Ed and Ania for their sake. Living in between would be awful, he argued, especially when raising a family. Gary suggested that Ed apply for a BME position here in order to combine departmental and candidate interests in securing a solid career path. That done, the resolution of a dual recruitment between Biomedical Engineering and Neurobiology and Anatomy, with collaborative labs, became clear. The outcome, as Gary puts it, has "been terrific for everyone involved."
Indeed! And to end the newsletter on more evidence of a great collaboration, little Robert will soon have a little brother to run around the yard with
Meliora,
David S. Guzick, MD, PhD
Dean, School of Medicine and Dentistry
