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Robert Murphy – intelligent computers and insights into cells

Will humans, who consist of billions of cells and hundreds of billions of molecules, ever understand their own complexity? Robert F. Murphy, External Senior Fellow at the Freiburg Institute for Applied Sciences (FRIAS), is a pioneer in what is known as computational biology. This discipline uses mathematical and computational methods to investigate the complexity of biological systems. Progress in this discipline is of major importance for medical and pharmaceutical research as well as the agricultural industry.

Prof. Dr. Robert F. Murphy © FRIAS

Brainstorming is one of his main activities. Robert F. Murphy is External Senior Fellow at the School of Life Sciences - LifeNet at the Freiburg Institute for Applied Sciences (FRIAS). The Ray and Stephanie Lane professor for computational biology is also professor of biological sciences, biomedical engineering and machine learning at the Carnegie Mellon University in Pittsburgh (USA).

His American research group focuses mainly on how it is possible to objectively determine the subcellular location of proteins. Proteins are one of the most important classes of molecules; they either constitute the cytoskeleton that determines the shape of cells, control the communication with other cells or mediate metabolic processes. "Systems biologists attempt to capture the entire range of complex dynamic interactions between the molecular players of a cell," said Murphy going on to add that "this is only possible when the researchers know the distribution and localisation of the subcellular molecular partners." Mathematics and computer sciences are indispensable tools for such investigations.

Plant growth and human diseases

Murphy has been working on this issue for quite some time. After obtaining his biochemistry degree from Columbia University in New York in 1974, he became interested in the mechanisms that control the transport of membrane proteins inside cells. His doctoral thesis, which he did at the California Institute of Technology in Pasadena, focused on the paths of transport vesicles inside cells. He used a fluorescence microscope to visualise dye-labelled molecules. Back then, cell biologists relied solely on their eyes to interpret the brightly shining microscope images. “I spent years waiting for somebody to come up with tools to allow me to analyse this type of images in an automated, and hence objective, way,” said Murphy. “But nobody ever did, so I decided to do it myself.” Nowadays, Murphy mainly concentrates on mathematics and programming. In his spare time he relaxes from his intellectual pursuits by playing baseball and going to baseball games, especially when he is back home in America.

At FRIAS, Murphy works closely with the research group led by Klaus Palme, an Internal Senior Fellow. In 2008, Murphy was awarded the Humboldt Research Prize which enabled him to spend the summer months in Freiburg. During this time, Palme and Murphy designed experiments involving plant cells that would enable them to discover the effect of certain pharmaceutical compounds on the subcellular location of certain proteins. This issue is also of great importance for agriculture as experiments like these enable researchers to identify proteins that lead to plant diseases or promote plant growth. Since many human diseases are caused by the defective distribution of proteins, Murphy envisages that the method might also be of benefit to the pharmaceutical industry. “The use of plant cells was very exciting since we had previously only used animal cells to test our methods,” said Murphy going on to add “green cells are far more complicated due their much greater morphological diversity.”

Computers will become increasingly important in the life sciences

Fluorescence microscope image of plant protoplasts taken with an automated procedure. The colour red indicates that the protoplasts are chloroplasts. The colour blue represents dead cells and green indicates the position of a genetically labelled protein (talin). © Joshua Kangas / Dr. Roland Nitschke (ZBSA Freiburg)

Murphy developed a computer programme that can find its way around the extremely heterogeneous "landscapes" of the microscopic images of plant cells. The programme calculates subcellular location features (SLFs), which are numerical features used to describe subcellular protein distributions. "SLFs are features that provide a numerical description of protein localisation. There are three sets of features, i.e. one that describes the closeness of an object to the centre of the image, another that describes more complicated aspects such as image texture, and a third that describes some other specific features. These features can be combined into different SLF sets." Initial experiments have been successful and the researchers will now focus on automating the preparation of plant cells. They envisage using a robot to isolate plant cells via a standardised method. This would be of enormous benefit for high-throughput experiments that are used to investigate complex biological systems. 

Murphy is sure that computers will eventually play an increasing role in the life sciences. And this is already the case with the first big epistemological issue. "I do not believe that human intuition will ever be able to understand the human being in his entire complexity. "In future, humans will continue to design experiments and models, but, due to the complexity of the problem, the decision as to which experiment or model to select will be taken by machine learning systems."

Murphy really enjoys his time in Freiburg and appreciates FRIAS' hospitality. In addition, he finds that the time he spends in Freiburg is of great value for him, particularly in terms of his science. "My time at FRIAS brings me a step closer to my goal," said the researcher referring to his plans to develop an automated machine learning system that will enable him to model the location of any protein at any given time and under any condition." Personally, his prime motivation is not the philosophical thirst for knowledge. "My main aim is to be able to contribute to the treatment of diseases," said Murphy. His discipline will undoubtedly contribute a great deal to reaching this objective.

Further information:
Prof. Dr. Robert F. Murphy
Freiburg Institute for Applied Studies (FRIAS)
School of Life Sciences – LifeNet 
Room 00 0012
Albertstr. 19
791004 Freiburg
Tel.: +49-(0)761/203-97418
Fax: +49-(0)761/203-97451
Email: robert.murphy(at)frias.uni-freiburg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/robert-murphy-intelligent-computers-and-insights-into-cells