Florigen’ Enters the Molecular Flowering

REVIEWS TIBS 25 – MAY 2000

of day length, whereas Maryland Mammoth requires a minimal length of night (short-day conditions) to induce ‘Florigen’ enters the molecular flowering. This discovery led to higher plants age: long-distance signals that being classified as long-day, short-day or day-neutral plants according to their response to particular photoperiods. cause plants to flower Obligate long-day and short-day plants have an absolute requirement for photoperiod signals to cause flowering, whereas day-neutral plants (also called autonomously flowering plants) will Joseph Colasanti and Venkatesan flower after making a particular number of leaves; that is, after they attain a par- Sundaresan ticular size. Most plants use a combination of environmental signals and The transition from vegetative to reproductive growth is a critical event in autonomous developmental signals to the life cycle of plants. Previous physiological studies have deduced that induce flowering at the appropriate time hormone-like substances mediate this important transition but the bio- (Fig. 1). It is important to emphasize chemical nature of the putative signaling molecules has remained elusive. that, in both environmentally responsive Recent molecular and genetic studies of key flowering-time genes offer and autonomous plants, the signals that new approaches to understanding the mechanisms underlying the initiation regulate the transition to flowering origi- of flowering. nate outside the SAM; in both cases, they probably originate in the leaves4,5. PLANTS HAVE ADOPTED unique devel- The transition to flowering is a flexible An important consequence of the dis- opmental mechanisms that allow process covery of photoperiodism was that the them to make the commitment to flow- The life of higher plants is broadly di- transition to flowering could be precisely ering in response to external signals. vided into a vegetative phase and a re- controlled. Many experiments aimed at The key structure that provides this productive phase. The SAM initiates characterizing the leaf-generated floral flexibility is the shoot apical meristem structures such as leaves during vegeta- stimulus were performed by using ei- (SAM), which gives rise to the aerial tive growth and inflorescences and flow- ther long-day or short-day plants that structures of the plant, such as leaves, ers during reproductive growth. The responded to a single stimulus. This re- stems and, ultimately, flowers1. transition to flowering, when a plant search was inspired by the concurrent The principal functions of the SAM switches from vegetative to reproduc- findings that most plant-growth regula- are: (1) to initiate the formation of lat- tive growth, is a pivotal event in the life tors, such as auxins, cytokinins and eral organs and structures, such as of a plant. Developmental signals that ethylene, are relatively simple chemical leaves and flowers; and (2) to perpetu- cause this transition to flowering origi- compounds that are freely mobile ate itself by maintaining a population of nate outside the SAM (Fig. 1), and so the within all plants6. The quest for a bio- undifferentiated cells that remain un- SAM remains uncommitted to flowering chemically defined floral stimulus was committed to a specific program. This prior to its perception of external sig- spearheaded by M.K. Chailakhyan, who ability of the cells in the SAM to remain nals. Floral induction causes a cascade coined the term ‘florigen’ to describe a uncommitted to flowering at a particu- of processes within the SAM that result hypothetical substance that induces lar time endows the plant with a great in its restructuring, accompanied by flowering in all higher plants7. deal of developmental flexibility. The changes in the rate and pattern of cell Most experiments involved grafting transition from vegetative growth to division, and the formation of floral leaves from plants exposed to flower- flowering is a clear illustration of the structures instead of leaves2. inducing photoperiods onto plants that importance of this. However, signals that had not been induced. It was found that originate outside the SAM are essential for Regulation by photoperiod and the search a signal of measurable mobility moved directing the conversion to reproductive for ‘florigen’ from leaf to SAM to cause the transition development. In this article, we describe The ability of signals that originate to flowering. In this way, the ‘velocity’ recent progress in discerning the nature outside the SAM to direct the develop- of signal movement was found to of the external signals that are responsible ment of the SAM allows plants to coordi- be ~2.4–3.5 mm hϪ1, depending on the for the transition to flowering. nate flowering time with environmental species7. These experiments showed conditions that favor successful polli- that the floral stimulus had the proper- J. Colasanti is at the Plant Gene Expression nation and seed production. Studies of ties of a mobile growth regulator but a Center and the Department of Plant and the biochemical nature of these external biochemically defined substance with Microbial Biology, University of California, signals followed an important discovery florigenic activity has never been iso- Berkeley, 800 Buchanan St, Albany, CA by Garner and Allard of a mutant variety lated. Consequently, it has been pro- 94710, USA; and V. Sundaresan is at the of tobacco, Maryland Mammoth, that posed that florigen might be not a single Institute of Molecular Agrobiology, 1 Research Link, The National University of flowers only when exposed to a particular molecule but a combination of different 3 Singapore, Singapore 117604. day length . The wild-type tobacco used known hormones and metabolites or Emails: [email protected]; in their experiment normally flowers assimilates that can vary among plant [email protected] after attaining a particular size, regardless species8. 236 0968 – 0004/00/$ – See front matter © 2000, Elsevier Science Ltd. All rights reserved. PII: S0968-0004(00)01542-5 TIBS 25 – MAY 2000 REVIEWS

A genetic approach to the ‘florigen’ problem Although early physiological studies failed to identify flower-inducing compounds explicitly, they laid the ground- work for a molecular and genetic ap- Environmental proach to understanding the mechanisms (e.g. photoperiod) underlying the transition to flowering. Studies by Murfet and co-workers com- bined grafting with genetic experiments to bridge physiological and genetic 9 studies . Working with the pea plant, Leaves they identified several genes that are required to mediate the transition to Signal flowering. Some of these genes act in source leaves to produce a floral stimulus (or Developmental to inhibit a promoter of vegetative (e.g. plant size) growth), whereas other genes function at the SAM to mediate responsiveness to external signals. Genes that might produce floral inhibitors or ‘antiflori- gens’ were also identified. The identifi- Vasculature cation and characterization of several Signal loci that control flowering in pea has re- movement vealed a complex picture of intercon- nected pathways but there is, to date, no molecular information on the rele- vant genes and their expression. Arabidopsis. More-recent insights about the regulatory networks controlling flowering have come from genetic and molecular studies of the model plant Arabidopsis. As flowering-time genes in SAM Arabidopsis have been reviewed exhaus- tively in recent articles9,10, only a brief Signal summary will be presented here. target Mutants in the flowering-time genes have defined three main pathways that regulate the flowering transition in Ti BS Arabidopsis: a day-length response pathway, an autonomous promotion pathway Figure 1 A simplified model of the components of the floral induction pathway. External stimuli (wavy and a gibberellin (GA) phytohormone arrows) are perceived by leaves and cause the floral inductive signals to be formed (orange pathway. arrows). Environmental stimuli (e.g. photoperiod) originate outside the plant, whereas de- Flowering time in Arabidopsis is accel- velopmental stimuli (e.g. leaf number, plant size) are intrinsic to the leaf. Potential signaling erated significantly by exposure to long molecules that are produced in the leaf can move via plasmodesmata (the intercellular por- days. There are two components to this tals) and flow into the vasculature (blue), where they are transported to the shoot apical day-length response pathway – light meristem (SAM; green). When inductive signals reach a SAM that is competent to flower, developmental events associated with the transition to flowering occur. quality and the circadian clock. The plant’s perception of these are mediated by phytochromes and cryptochromes11–13. The second pathway is the au- factors18,19. The third pathway that pro- Phytochrome regulation of flowering tonomous promotion pathway, which is motes flowering in Arabidopsis involves has been studied extensively, although required for flowering in response to in- the phytohormone GA, which is re- it is only recently that components of ternal developmental signals (e.g. the quired for early flowering in Arabidopsis the clock regulation of flowering have decision to flower after making a fixed but not in all plant species. It has been been identified. These include the number of leaves). Several genes in this shown that no other flowering path- cloning and characterization of the GI- pathway have been described and re- ways operate in Arabidopsis by making GANTEA gene, which provides a key link viewed elsewhere9. The autonomous a triple mutant in which genes from between the clock genes and the flower- promotion pathway can be substituted each of the three pathways have been ing genes14,15. It appears that the gene for by vernalization (the exposure of ger- knocked out: the resultant plants CONSTANS (CO) is the downstream tar- minated seeds to low temperatures). It are completely unable to flower get of both the light and the clock sig- appears that the autonomous pathway (G. Coupland, pers. commun.). nals14. CO encodes a zinc-finger tran- and vernalization operate through the An important regulator of the final scription factor, and ectopic expression same downstream regulatory gene, stages of flowering is the LEAFY gene, of CO causes early flowering under FLF/FLC, which encodes a protein similar which encodes a transcription factor20. short days16,17. to the MADS-domain class of regulatory LEAFY, which is itself a presumed target 237 REVIEWS TIBS 25 – MAY 2000

However, because it is synthesized throughout the plant, it appears un- likely to serve as the long-distance flowering signal. Moreover, the fact that Arabidopsis GA mutants can still flower in response to photoperiod implies that the day-length pathway must use a signal other than GA. Thus, despite the impres- sive amount of knowledge obtained on the genetic control of flowering in Arabidopsis, there is very little information about the identities of the genes and signals involved in communicating from the leaves to the SAM to initiate the flowering transition. Maize. A key flowering-time gene recently isolated from maize could provide the first clues about the molecular nature of floral inductive signals27. Maize plants that have mutations in the indeterminate gene (id1) are unable to undergo a normal transition to flowering; rather, the SAM of id1 mutants con- tinues to initiate leaves long after normal plants have flowered (Fig. 2). Eventually, id1 mutants do undergo the transition to flowering but they produce aberrant floral structures with vegetative characteristics27,28. The id1 gene was found to encode a putative transcriptional regulator27, similar to what Normal id1/id1 has been found in Arabidopsis, in which

Ti BS many of the late-flowering genes that have been isolated have possible regulatory functions. Figure 2 However, the expression pattern of Consequences of the loss of id1-gene function. The shoot apical meristem (SAM) of a nor- id1 is unlike the expression patterns of mal maize plant (left) initiates a predictable number of leaves and then makes the transition to flowering. The SAM is converted into the tassel or male inflorescence (blue oval) and any of the flowering-time genes found in one or more axillary meristems develop into ears or female inflorescences (pink ovals). By Arabidopsis. The id1 mRNA is restricted contrast, an id1 homozygous mutant plant (right) remains in a state of vegetative growth for to a specific domain: id1 transcript is de- a prolonged period of time and makes many more leaves than a normal plant. tected only in young leaves27 (Fig. 3). The presence of id1 in leaves and its ab- sence in the SAM suggests that the id1 of the flowering-time regulators17, acts expressed uniformly in both leaves and gene does not act at the SAM to mediate at the SAM and surrounding leaf primor- in the SAM16,17. This is consistent with a the transition to flowering. Rather, id1 dia to activate APETELA1 and floral role for CO at any step from the produc- could have a role in regulating the pro- homeotic genes required for flower de- tion or transmission of a leaf-generated duction of a floral stimulus or, perhaps, velopment21,22. Expression studies sug- signal to reception of the signal at the in repressing the activity of a floral gest that LEAFY plays a central role in SAM. The action of the autonomous pro- inhibitor. The specific function of id1 is integrating external floral-inductive sig- motion pathway might not require the not known; the predicted protein se- nals received at the SAM with the devel- existence of leaf-to-SAM signals, and quence reveals that ID1 contains zinc- opmental events of flower formation23,24. there is currently no evidence for such a finger motifs related to transcriptional The day-length pathway operates signaling mechanism in Arabidopsis. regulators found in animals27. Therefore, through signals that are perceived in the Nevertheless, it is interesting that the id1 probably regulates the activity of leaves (photoperiod) but affect the FCA gene, which encodes a regulatory other genes. Establishing the function of SAM, implying that signal transmission RNA-binding protein25, has been shown ID1 awaits the identification of down- must be an important part of its action. to act non-autonomously over cell lay- stream target genes. However, there is no evidence that any ers, which raises the possibility that it The finding that ID1 might act in leaves of the genes from this pathway that regulates a diffusible flowering signal26. reinforces studies by Irish and co-work- have been characterized to date play a However, FCA, like CO, is expressed ers, who studied the effects of physically specific role in generating or transmit- ubiquitously, making it difficult to deter- separating the SAM from the rest of the ting the signal. For example, the key CO mine its site of action. plant29,30. Maize plants from a particular gene, the downstream target of the pho- GA is diffusible and thus would be a inbred line make a fixed number of leaves toperiod and clock-perception genes, is potential candidate for a flowering signal. and then flower. By surgically removing 238 TIBS 25 – MAY 2000 REVIEWS and rerooting the SAMs of growing unpublished) (Fig. 3). That is, as plants, they showed that the cells (a) (b) leaves emerge and become photo- of the apex were not committed to synthetically active (i.e. become produce a particular number of 200 source tissues), id1-mRNA levels leaves: SAMs that were excised decrease. This correlation sug- made more leaves before flowering gests a possible mechanism by than SAMs left connected to the 100 which, instead of regulating the rest of the plant. However, addi- production of the floral stimulus, tional leaves were not made if a the ID1 protein could control the 50 critical number of leaves were ex- transmission of the signal by regu- cised along with the SAM. There lating its flow in the developing are two important conclusions 20 leaves. Further studies of ID1 func- from these studies. First, the maize tion are needed to investigate this SAM can be reprogrammed to gen- possibility. erate different numbers of leaves At least one study has shown 10 high prior to flowering. Second, leaves id1 mRNA that changes in the flow of small levels must be capable of signaling the none molecules into the SAM occur dur- SAM to switch to reproductive 5 ing the transition to flowering in growth at a specific developmental Arabidopsis. Using fluorescently la- stage; that is, leaves are the likely beled tracers, Gisel and co-workers source of the flowering stimulus. leaf showed that the movement of mol- 1 There are many notable dif- ecules greater than a particular size ferences between maize and SAM were excluded from the Arabidopsis Arabidopsis with respect to flow- SAM just before the transition to Ti BS ering time. Flowering in maize is flowering35. Whether controlling the nearly autonomous, with the de- Figure 3 movement of assimilates and other velopmental stage being a more (a) The id1-mRNA localization pattern of a maize molecules from one part of the significant determinant of flower- seedling that is approaching the transition to flower- plant to another is an important ing time than environmental con- ing, showing where this diagram is in relation to the regulator of flowering time will be ditions. By contrast, flowering whole plant (b). The SAM is at the bottom center, sur- determined by further experiments. in Arabidopsis is greatly acceler- rounded by developing leaves, with leaves initiated Another possible mechanism by the SAM elongating and growing outwards from this ated by long-day photoperiods. point. The id1 mRNA (red) is only detected within that could be invoked to explain the Furthermore, the phytohormone immature leaves of the growing plant. The apical transmission of long-distance sig- GA has little effect on flowering portions of the leaves are more mature than the basal nals is gene silencing36. Studies with time in maize: flowering is only regions and outer leaves are more mature than inner tobacco have found that epigenetic slightly delayed in maize GA mu- leaves. A log scale (in mm) shows the vertical dis- states of genes can be transferred tants. By contrast, in Arabidopsis, tance from the SAM to the ends of the leaves. A black from one part of the plant to dotted line indicates the approximate point at which GA is a major regulator of flower- the leaves emerge from the whorl; this is correlated another via plasmodesmata and 37 ing. Therefore, it is important to with the time in leaf development at which leaves phloem channels ; for example, an recognize that genes implicated in change from sink to source tissues. ectopically applied marker gene flowering in one plant species was able to silence the expression of could have a very different an endogenous gene37. An interest- function in a heterologous species. molecules from source tissues to sink tis- ing similarity to the mobile floral stimulus Presumably, as more flowering-time sues. Source tissues include expanded, is that the endogenous gene was silenced genes are isolated from Arabidopsis and mature leaves that fix carbon by photo- first at the site of the ectopic gene’s appli- other plants, genes that function specifi- synthesis, whereas sinks are non-photo- cation in the leaf and then the effect cally to control long-distance flowering synthetic tissues such as roots, imma- slowly migrated throughout the plant. signals will be identified. ture leaves and floral organs that rely on Although gene silencing is thought to be source tissues to supply fixed carbon31,32. important for subduing invading viral The transmission of long-distance flowering Another control point in the transi- genes, an intriguing possibility is that signals: a plumber’s perspective tion to flowering could operate by regu- mobile gene silencing, from leaf to apex, Until now the discussion of the transi- lating the flow of signals from the leaves could provide the developmental signals tion to flowering has centered around to the SAM. Current studies of the struc- that cause the transition to flowering. If two components of the system – the ture of plasmodesmata, the portals be- this were the case, it would explain the leaves of the plant, where the flower in- tween plant cells (and the functional difficulty in identifying florigenic com- ducing signals are produced, and the equivalent of animal-cell gap junctions), pounds, because such a signal could not SAM, the ultimate target of the signals. show that the intercellular movement of be isolated biochemically. However, another component that should small molecules within the leaf changes be considered is the signal-transport during the sink-to-source transition33,34. Outlook system (Fig. 1). Early physiological It is interesting to note that the id1- Early attempts to isolate and to char- studies showed that mobile signals trav- mRNA expression pattern in young acterize flower-inducing compounds by elled in the vasculature of the plant; leaves corresponds to the transition in biochemical means are giving way to the specifically, through the phloem, which the apical portions of the leaves from molecular characterization of the genes also transports nutrients and other sink to source tissues33 (J. Colasanti, that control the transition to flowering. 239 REVIEWS TIBS 25 – MAY 2000

Although at an early stage, the genetic mechanisms that control the transition 16 Putterill, J. et al. (1995) The CONSTANS gene of Arabidopsis promotes flowering and encodes a protein networks that interact to control flower- to flowering. showing similarities to zinc finger transcription factors. ing are being elucidated by analysing Cell 80, 847–857 17 Simon, R. et al. (1996) Activation of floral meristem flowering-time genes from Arabidopsis, Acknowledgements identity genes in Arabidopsis. Nature 384, 59–62 maize and other species. As more genes We thank Paula McSteen, Yukiko 18 Sheldon, C.C. et al. (1999) The FLF MADS box gene: a are isolated, their function will be de- Mizukami and Leonore Reiser for dis- repressor of flowering in Arabidopsis regulated by vernalization and methylation. Plant Cell 11, 445–458 fined in terms of where they act in the cussions and comments on this 19 Michaels, S. D. et al. (1999) Flowering locus C encodes a floral induction pathway and whether manuscript, and Fred Hempel for helpful novel MADS domain protein that acts as a repressor of flowering. Plant Cell 11, 949–945 they mediate environmental signals or discussions. Research by J.C. is sup- 20 Weigel, D. et al. (1992) LEAFY controls floral meristem control autonomous signals. A new per- ported by grants from the National identity in Arabidopsis. Cell 69, 843–859 21 Busch, M.A. et al. (1999) Activation of a floral homeotic spective on this problem is to consider Science Foundation (MCB-9630622 and gene in Arabidopsis. Science 285, 585–587 the plant as a multicomponent system MCB-9982714) and Pioneer Hi-bred 22 Wagner, D. et al. (1999) Transcriptional activation of APETALA1 by LEAFY. Science 285, 582–584 comprising the SAM (the target of the International. 23 Blazquez, M.A. et al. (1997) LEAFY expression and flower signal), the leaf (the floral-signal genera- initiation in Arabidopsis. 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18th International Congress of Biochemistry and Molecular Biology: Beyond the Genome (16–20 July 2000, Birmingham, UK)

There are two types of travel grants available for financial assistance to attend this conference, the Millennium Travel Fund and the IUBMB/FEBS 2000 Biochemical Society Student Travel Fund. Visit the conference web site for more details (http://www.iubmb2000.org).

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