Howe Lab - Research Overview
This section summarizes the work going on in the lab. The links to individual people's web pages give you more information on particular areas. Our work covers a number of areas in the biochemistry and molecular biology of photosynthetic organisms, and the evolutionary processes that gave rise to them. We trace the lineage of our interest in photosynthesis to Robin Hill, one of the great pioneers of photosynthesis biochemistry, and our interest in the chloroplast genome and its evolution to Fred Sanger and his application of his DNA sequencing methodology to the mitochondrial genome.
Our present interests lie in three main areas. Although they may seem distinct, in reality they are very complementary. These areas are:
We were founder members of the Algal Bioenergy Consortium, an interdisciplinary group of scientists aiming to use algae for a number of different applications in the bioenergy industry.
We also have close links with Martin Jones, Mim Bower, Harriet Hunt and Diane Lister of the McDonald Institute for Archaeological Research, studying a range of archaeogenetic questions. Please look at their entries on this site or the McDonald Institute for more information.
There are possibilities for PhD and postdoctoral work in all the areas described below. Please contact Prof Howe for more information.
Double Nobel Laureate Fred Sanger opening the refurbished Plant Biochemistry lab
Photosynthesis biochemistry pioneer Robin Hill
The figure below shows a schematic representation of the electron transfer chain in cyanobacteria. (These are oxygenic photosynthetic bacteria, also known as blue-green algae, and are responsible for a large part of global oceanic productivity.)
The electron transport chain in cyanobacteria. © CJH 2005
The figure shows the two photosystems (PSI and PSII) linked by the cytochrome b6f complex. Two soluble electron carriers can accept electrons from cytochrome f. These are plastocyanin, which contains copper, and cytochrome c6, which contains haem. Cytochrome c6 substitutes for plastocyanin under conditions of copper deprivation. In chloroplasts of higher plants, the situation is simpler. There is no cytochrome oxidase and, if you believe the text books, there is no cytochrome c6. However, in 2002, we and a group in Berkeley independently reported that there is a cytochrome c6 in plants, which we have named cytochrome c6A. More recently, we have shown cytochrome c6A exists in the green alga Chlamydomonas, too. We have shown that this protein does not function as a simple substitute for plastocyanin in photosynthetic electron transfer - but its real function remains a mystery, which we are working to solve. A key to this is likely to be the presence in cytochrome c6A of an insertion containing two conserved cysteine residues (marked in yellow in the figure below).
Predicted structures of plant cytochrome c6A (left) and the well-characterized cyanobacterial protein (right). Picture produced by Derek Bendall © CJH 2005.
Algae and cyanobacteria offer very exciting prospects for renewable energy production. We are interested in manipulating them for this, either by simple manipulation of environmental conditions, or by genetic modification. Along with the group of Dr Adrian Fisher in Cambridge, we have pioneered the development of "biophotovoltaic" devices. These contain algal or cyanobacterial cells in a compartment containing an electrode and a mediator, such as potassium ferricyanide. On illumination, electrons are passed from the photosynthetic electron transfer chain and thence to the electrode. They then flow through a circuit to the second compartment in the device. Depending on how the device is configured, it can be used primarily for current generation, or for hydrogen production in the second compartment.
Algal cells and an example of the biophotovoltaic device. © CJH 2010.
Chloroplasts of plants and algae contain a genome that is the remnant of the genome of the photosynthetic bacterium that gave rise to chloroplasts some 1.5 billion or more years ago. This genome is typically about 150 kbp in size and contains 120 or more genes, encoding polypeptides of the photosynthetic machinery, as well as proteins and RNAs required for their expression and many other functions. Understanding the organization and expression of the chloroplast genome is a long-standing theme in the lab.
The last major group of organisms to have their chloroplast genome characterized was the dinoflagellate algae. These ecologically important organisms are responsible for red tides (when their prolific growth turns oceans red), many instances of shellfish poisoning, and significant oil deposits. In addition, they are symbionts with coral cells, and provide the corals with nutrient. An important group of the dinoflagellate algae (which contain a light-harvesting pigment called peridinin) have a chloroplast genome completely different from other algae and plants.
The marine dinoflagellate Amphidinium carterae (size approximately ten microns). Photo by Edmund Nash © CJH 2004
Adrian Barbrook in our group showed recently that the dinoflagellate Amphidinium operculatum has lost the conventional chloroplast genome. Most of the genes usually found there are believed to have moved to the nucleus. The rest are located on small plasmids or 'minicircles' of about 2.5 kbp, most of which contain a single gene - though some have two or three, and there are also 'empty' minicircles that have none! The dozen or so genes that the chloroplast has retained encode components of the light reactions of photosynthesis.
We are interested in understanding how these minicircles are maintained, where they are located, and how other proteins re-enter the chloroplast. The minicircles may be useful genetic markers for different strains of coral symbionts, and help us to understand the process of 'coral bleaching', when corals expel their dinoflagellate symbionts, with catastrophic results. The discovery of this highly reduced chloroplast genome also raises questions about why genes have moved from chloroplast to nucleus during evolution, and why some have been retained in the chloroplast.
A big surprise in recent years in work on chloroplast DNA was the demonstration that Plasmodium, the organism that causes malaria, has a remnant chloroplast and was once a (presumably free-living) photosynthetic protozoan. This chloroplast, which is still essential for Plasmodium to survive, represents an attractive target for antimalarials. We are interested in understanding the expression and control of the Plasmodium chloroplast genome.
We have a long-standing interest in using sequence data to answer questions in evolutionary biology, such as whether a single endosymbiosis was ultimately responsible for all chloroplasts (whether of green, red or brown algae), or whether multiple primary endosymbioses have occurred. This is not a straightforward question to answer because of the difficulty of modelling accurately the evolution of sequence data over more than a billion years. We discuss these problems critically in "The origin of plastids" (Phil. Trans. Roy. Soc. B 363 2675-2685 (2008)). We are also studying other early events in evolution, such as the divergence of eukaryotes, and have used the components of the TSC1/TSC2/TOR signalling pathway as markers for this.
We have a particular interest in novel applications of phylogenetic techniques, especially in studying the texts of manuscripts. In the days before printing, manuscripts were copied by scribes, who introduced changes - either deliberately or accidentally. For a long time, scholars have used the distribution of variations among different extant versions of a text to determine which were copied from the same earlier version and produce a stemma (plural: stemmata), a tree showing these relationships. This is known as stemmatic analysis, and was pioneered by the German scholar Karl Lachmann in the 19th century.
The scribe Jean Mielot (from 'Scribes and Illuminators', C. de Hamel, British Museum Press).
The accumulation and propagation of changes to a text during copying has clear parallels with the accumulation and propagation of mutations in DNA sequences during replication, and the construction of phylogenetic trees. We showed some time ago that computer programs used for phylogenetic analysis of sequence data could also be used very easily to analyse the texts from medieval manuscripts and produce stemmata that were consistent with the ideas of manuscript scholars.
Phylogenetic analysis of the Prologue to The Wife of Bath's Tale, in Chaucer's Canterbury Tales (from Barbrook AC, Howe CJ, Blake N & Robinson P (1998) Nature 394 839). Each two- or three-letter symbol is a different extant manuscript. The groups A-F, O indicate clusters identified by conventional scholarship. © CJH 2005
We now have active collaborations with scholars working on manuscripts ranging from the Canterbury Tales to the Greek New Testament to test and refine the use of phylogenetic programs in studying the evolution of texts. An area of particular interest is contamination, where a scribe used more than one source simultaneously when making a copy. You can see this in the picture above, where the scribe has a second book open, as well as the one he is copying from directly. This is analogous to recombination and lateral gene transfer, and we are looking at the applicability of network phylogenetic techniques and other methods for studying manuscripts that show contamination. For more information on this, see Heather Windram's page. Funding for PhD and other places in such an interdisciplinary topic is not always easy to arrange, but the application of network phylogenetic techniques to manuscripts is a very promising area, and we have many different sets of manuscripts to study.
About the lab
The lab is based in the Cambridge University Biochemistry Department, on the Downing Site (a cluster of mainly biological research departments) in the centre of Cambridge. We are a group of about 8-10 people, mostly postdocs and PhD students. Wendy Gibson, the laboratory manager, maintains the lab facilities. At certain times of year there are also undergraduate project students. Prior experience of working with plants or algae is not necessary for joining the group. At present our funding comes mostly from the Engineering and Physical Sciences Research Council, the Leverhulme Trust, and from industry. We have had a number of summer students with bursaries from the Nuffield Foundation and other organizations.
We have active collaborations with a number of labs worldwide as well as in the UK, including elsewhere in Europe, China, Australia, and New Zealand. We have weekly lab meetings, at which members of the group present their work to the rest of us over coffee and cake (a substance that forms an important part of the lab social life). From time to time we go off on a "lab jolly". Recent jollies have included day trips to France, visits to the seaside, a nuclear power station, a brewery and a sewage works.